The emergence of antibiotic-resistant bacteria has attracted interest in the field of endolysins. Here, we analyzed the diversity of Streptococcus endolysins and identified a new endolysin, Ply2741, that exhibited broad-spectrum bactericidal activity. Our results demonstrated that Ply2741 could effectively eradicate multidrug-resistant gram-positive pathogens in vitro and in vivo. Structural analysis revealed that the bactericidal activity of Ply2741 depends on the classic "Cys-His-Asn" catalytic triad. Site-directed mutagenesis results further identified that the conserved residue Gln29, located near the catalytic triad, also contributes to the lytic activity of Ply2741. Furthermore, the key residues (R189 and W250) in the Ply2741 cell wall binding domain (CBD) responsible for binding to peptidoglycan were revealed by molecular docking and fluorescence-activated cell sorting (FACS) analysis. Ply2741 demonstrates a broad lytic spectrum, with significant bactericidal activity against Enterococcus, Staphylococcus, and Streptococcus and species. To the best of our knowledge, we found that residue Gln29 participated in the lytic activity of endolysin for the first time. Additionally, we systematically elucidate the binding mode and key residues of the Ply2741CBD. This study proposes Ply2741 as a potential antibiotic substitute and provides a structural basis for the modification and design of endolysins.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a major global health threat due to its resistance to conventional antibiotics. The commensal microbiota maintains a symbiotic relationship with the host, playing essential roles in metabolism, energy regulation, immune modulation, and pathogen control. Mammals harbor a wide range of commensal bacteria capable of producing unique metabolites with potential therapeutic properties. This study demonstrated that M28 family peptidase (M28), derived from commensal bacteria Peribacillus frigoritolerans (P. f), provided protective effects against MRSA-induced pneumonia. M28 enhanced the phagocytosis and bactericidal activity of macrophages by inducing trained immunity. RNA sequencing and metabolomic analyses identified the CFB-C3a-C3aR-HIF-1α axis-mediated phosphatidylcholine accumulation as the key mechanism for M28-induced trained immunity. Phosphatidylcholine, like M28, also induced trained immunity. To enhance M28-mediated therapeutic potential, it was encapsulated in liposomes (M28-LNPs), which exhibited superior immune-stimulating properties compared to M28 alone. In vivo experiments revealed that M28-LNPs significantly reduced bacterial loads and lung damage following MRSA infection, which also provided enhanced protection against Klebsiella pneumoniae and Candida albicans. We first confirmed a link between complement activation and trained immunity, offering valuable insights into the treatment and prevention of complement-related autoimmune diseases.

Staphylococcus aureus is a leading cause of bacterial-induced mortality due to infections that are increasingly resistant to antibiotics, highlighting the need for new therapeutic strategies to treat these drug-resistant infections. Targeting essential pathways that differ from the host, such as cell wall synthesis, has served as an effective approach for antimicrobial drug development. Nucleotides are essential building blocks for nucleic acids and the bacterial cell wall, and we hypothesized that the metabolic pathways required to obtain these molecules may represent promising antimicrobial targets. To investigate if pyrimidine metabolism could be leveraged to inhibit S. aureus growth, we tested the antimicrobial activity of the uracil derivative, 4-thiouracil (4-TU). Growth of laboratory methicillin-susceptible and resistant strains, including a methicillin-resistant clinical isolate, is inhibited by 4-TU. Based on the structural similarity between 4-TU and uracil, we hypothesized that 4-TU hijacks the pyrimidine salvage pathway for incorporation into RNA. High-performance liquid chromatography (HPLC) analysis showed 4-thiouridine (s4U) in RNA isolated from S. aureus treated with 4-TU. Isolation of 4-TU-resistant S. aureus suppressor strains revealed that mutations in uracil phosphoribosyltransferase (Upp), a component of the pyrimidine salvage pathway, confer resistance to 4-TU. HPLC analysis of RNA isolated from an S. aureus upp mutant demonstrated a lack of s4U, suggesting that upp is required for incorporation of 4-TU into RNA. Expression of Clostridioides difficile thiouracil desulfurase in S. aureus, or cotreatment with uracil and 4-TU, alleviates 4-TU toxicity. Collectively, these findings suggest that 4-TU commandeers the pyrimidine salvage pathway to inhibit S. aureus growth.

Staphylococcus aureus is associated with greater than one million global deaths annually and is capable of infecting every human tissue. The increasing emergence of antibiotic-resistant strains emphasizes the urgent need to develop new therapeutic strategies to treat infections. Nucleoside analogs that disrupt pyrimidine or purine nucleotide metabolism serve as a promising approach for treating drug-resistant infections, as these pathways differ between host and bacteria. Here, we demonstrate that the uracil derivative 4-thiouracil (4-TU) inhibits S. aureus growth by hijacking the pyrimidine salvage pathway, leading to incorporation of 4-TU into RNA. We found that mutations in uracil phosphoribosyltransferase (upp) confer resistance to 4-TU and prevent incorporation into RNA. Expression of a thiouracil desulfurase (tudS) from Clostridioides difficile is sufficient to detoxify 4-TU and diminish 4-TU levels in RNA. Taken together, these results suggest that 4-TU-mediated disruption of pyrimidine metabolism limits S. aureus growth, which may serve as a promising therapeutic target.

The pathogenicity of Staphylococcus aureus is significantly attributed to its capacity to produce biofilms, which bolster bacterial resistance against antibiotics and host immune responses. This study aimed to explore the involvement of icaABCD genes in biofilm formation ability of S. aureus clinical isolates.

One hundred clinical S. aureus isolates were collected from hospitalized patients at a burn center in North of Iran. The isolates were identified using standard biochemical tests and confirmed by the presence of the nuc gene. Antibiotic susceptibility profiles were determined through the disk agar diffusion method. Biofilm formation capacity was determined using microtiter plate assay. PCR test was conducted to detect the presence of icaABCD genes.

Penicillin exhibited the highest resistance rate (94%), while vancomycin was most effective antibiotic with 6% resistance. Besides, 32% of the isolates demonstrated as multidrug resistant (MDR) and 29% were Methicillin-resistant S. aureus (MRSA). Notably, 89% of the isolates were identified as biofilm produces, while 54 (60.67%), 28 (31.46%), and 7 (7.86%) isolates exhibited strong, moderate, and weakly biofilm production ability, respectively. PCR results revealed a prevalence of 90%, 92%, 92%, and 94% for the icaA, icaB, icaC, and icaD genes, respectively. Intriguingly, the MDR isolates exhibited a 100% prevalence of these genes. Similarly, 96.55%, 89.65%, 89.65% and 96.55% of the MRSA isolates were carrying the icaA, icaB, icaC, and icaD genes, respectively.

This study revealed a noteworthy prevalence of biofilm-producing strains of S. aureus. High prevalence of icaADBC genes as well as highlighted capacity of the biofilm formation in MRSA and MDR strains exhibited a potential correlation between biofilm and antibiotic resistance patterns. Given the enhanced resilience of bacteria within biofilms against antibiotics, addressing biofilm production is imperative alongside antibiotic treatments for effective control and eradication of infections.

Staphylococcus aureus is the second most common pathogen found in all cases of nosocomial infections globally. Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of infection among preterm and critically ill newborns in neonatal intensive care units. Newborns are predominantly susceptible to S. aureus and MRSA colonization and infection due to their weaker immune systems. Treating infections in newborns associated with S. aureus and MRSA has proven challenging due to decreasing susceptibility to first-line antibiotics, leaving clinicians with few treatment options. This cross-sectional study aimed to determine the prevalence of hospital-acquired MRSA among neonates at the Dormaa Presbyterian Hospital in Ghana, the susceptibility profile to selected antibiotics, and the associated risk factors. Venous blood samples were taken from each of the neonatal participants and inoculated into Brain Heart Infusion broth. Standard biochemical tests were performed, and 36.0% (9/25) of the S. aureus isolates were identified as MRSA. The MRSA isolates were more susceptible to ciprofloxacin, levofloxacin, gentamicin, co-trimoxazole, tetracycline, and cephalexin but resistant to cloxacillin, ampicillin, roxithromycin, and lincomycin. The study found that gestational period (χ2 = 3.865, P = 0.049) and longer length of hospital stay (χ2 = 10.911, P = 0.012) were statistically significant for S. aureus and MRSA infection. Surveillance systems should be put in place by health authorities at the hospital, targeting decolonization of MRSA strains at the hospital as well as monitoring antibiotic resistance that occurs through inappropriate access and use of antibiotics.

The methicillin-resistant Staphylococcus aureus (MRSA) threat has become a source of concern for medical facilities and patients worldwide. MRSA infections are more difficult to treat, resulting in higher rates of morbidity and mortality. Prematurity, low birth weight, method of delivery, mode of resuscitation after birth, feeding method, prolonged hospital stay, kangaroo mother care, and overcrowding in hospitals are all risk factors for MRSA infection. Overcrowding is a common issue in the Dormaa Presbyterian Hospital (DPH), as it is in most hospitals around the country. The study intended to bring to the notice of mothers, hospital staff, and caregivers the risk factors associated with Staphylococcus aureus and methicillin-resistant Staphylococcus aureus among neonates at DPH.

Staphylococcus aureus (S. aureus) as common Gram-positive pathogenic bacteria, causes local and systemic infections, including sepsis and bacteremia. In particular, the high prevalence of drug-resistant S. aureus further complicates the post-infection treatment. Highly effective S. aureus vaccines are urgently desired. Herein, a novel S. aureus vaccine (MnO2@FS) is developed via biomineralizing manganese dioxide (MnO2) on formaldehyde-fixed S. aureus (FS). In such vaccine, with FS to induce bacteria-specific immune responses, MnO2 via releasing Mn2+ can activate the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway and innate immunity, which would be rather helpful to enhance immune responses against bacterial infections. It is found that bone marrow-derived dendritic cells (BMDCs) treated with MnO2@FS show higher FS and manganese uptake, and enhanced cytokine secretions. In mice, after being immunized with MnO2@FS, the level of S. aureus-specific antibody is significantly improved compared with FS and simple mixture of FS and MnO2 (FS+MnO2). Furthermore, MnO2@FS immunized mice can clear infected bacteria faster and showing higher survival rate in lethal models, outperforming FS and FS+MnO2 immunizations. In addition, the vaccine effectively controls abscess development in a hospital-acquired S. aureus infection model. This study thus presents a new strategy for the construction of highly potent yet safe bacterial vaccines.

Although contact precautions (CP) have proven effective in protecting patients and healthcare providers and preventing the transmission of methicillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities, pediatric patients under CP may experience unintended effects, including psychosocial stress and limited access to developmentally appropriate activities. Modifying or discontinuing the routine use of CP based on risk assessment results may enhance their overall benefits. Facilities that opt to modify or cease the routine use of CP should base their decisions on (1) compliance with the local regulations related to MRSA; (2) institutional compliance with CP for patients with MRSA infection and/or colonization, and (3) assessment of local MRSA data. Irrespective of any changes, all pediatric facilities should conduct ongoing assessments of MRSA-specific risks and monitor compliance with infection control practices. The results of these activities should guide the optimal use of CP to prevent MRSA infections among hospitalized pediatric patients.

Drug-resistant Staphylococcus aureus (DRSA) poses a significant global health threat, like bacteremia, endocarditis, skin, soft tissue, bone, and joint infections. Nowadays, the resistance against conventional drugs has been a prompt and focused medical concern. The present study aimed to explore the inhibitory potential of plant-based bioactive compounds (PBBCs) against effective target proteins using a computational approach. We retrieved and verified 22 target proteins associated with DRSA and conducted a screening process that involved testing 87 PBBCs. Molecular docking was performed between screened PBBCs and reference drugs with selected target proteins via AutoDock. Subsequently, we filtered the target proteins and top PBBCs based on their binding affinity scores. Furthermore, molecular dynamic simulation was carried out through GROMACS for a duration of 100 ns, and the binding free energy was calculated using the gmx_MMPBSA. The result showed consistent hydrogen bonding interactions among the amino acid residues Ser 149, Arg 151, Thr 165, Thr 216, Glu 239, Ser 240, Ile 14, as well as Asn 18, Gln 19, Lys 45, Thr 46, Tyr 109, with their respective target proteins of the penicillin-binding protein and dihydrofolate reductase complex. Additionally, we assessed the pharmacokinetic properties of screened PBBCs via SwissADME and AdmetSAR. The findings suggest that β-amyrin, oleanolic acid, kaempferol, quercetin, and friedelin have the potential to inhibit the selected target proteins. In future research, both in vitro and in vivo, experiments will be needed to establish these PBBCs as potent antimicrobial drugs for DRSA.

To investigate the genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis and correlate it with the presenting clinical features and outcomes.

Nine patients presenting with MRSA endophthalmitis from 2014 to 2022 were included. Phenotypic and genomic tests were used for strain characterization. Demographics, clinical presentation, treatment and outcomes were reviewed.

The MRSA population was dominated by multidrug-resistant (MDR) strains within the clonal complex 5 (CC5) carrying an SCCmec type II genetic element (USA100-like strains). These strains carried genes that confer resistance to five antibiotic classes, in addition to mutations in topoisomerase genes (gyrA and parC) that resulted in resistance to all fluoroquinolones tested. Patients were mostly male (56%), with a median age of 82.7 years, and most had no recent history of extensive healthcare exposure. All cases were exogenous following ocular surgery (67%) or intravitreal injection (33%). The main exam findings were visual acuity ≤ hand motion, hypopyon (89%), and vitreous opacity (89%). Five patients (56%) showed improvement in visual acuity at 1 month following presentation, three (33%) at 3 months, and two (22%) at 6 months. Complications included evisceration (n = 1) and phthisis (n = 1). Patients who had pars plana vitrectomy within 48 hours of presentation had better clinical outcomes compared to those who did not.

Exogenous MRSA endophthalmitis is caused by MDR strains that resemble the hospital-acquired lineage USA100. These strains cause severe endophthalmitis in patients with no recent hospital/healthcare exposure.

Staphylococcus aureus (S. aureus), particularly methicillin-resistant strains (MRSA), poses a significant threat to global public health due to its resistance to conventional antibiotics. The urgent need for alternative treatments has highlighted cepharanthine (CEP), a bisbenzylisoquinoline alkaloid, known for its antiviral, antibacterial, and anti-inflammatory properties. However, the clinical application of CEP is constrained by several factors. These include the requirement for a high therapeutic dosage, low aqueous solubility, restricted oral absorption, and a short half - life. In this study, we developed a chitosan-coated Poly Lactic-co-Glycolic Acid (PLGA) nanoemulsion encapsulating CEP (CCPN) using the double-emulsion solvent evaporation method. The formulation was optimized to achieve ideal physicochemical properties, including a particle size of 588.13 ± 31.87 nm and a zeta potential of 48.60 ± 1.00 mV, ensuring stability and uniformity. Biological evaluations demonstrated that CCPN effectively inhibited hemolysis, suppressed biofilm formation, disrupted mature biofilms, and displayed potent antibacterial activity against S. aureus. In vivo studies using a murine pneumonia model revealed that CCPN significantly alleviated lung damage, reduced bacterial load, mitigated inflammatory responses, and improved survival rates of mice infected with S. aureus or MRSA. These findings highlight CCPN as a promising therapeutic strategy for treating bacterial pneumonia. This novel nanoemulsion effectively tackles the key limitations in antimicrobial therapy by boosting the solubility, stability, and antibacterial efficacy of CEP. It holds great promise in the fight against antibiotic - resistant infections and shows substantial potential for promoting the treatment of pulmonary diseases.

Staphylococcus aureus is an opportunistic microorganism which can cause minor skin infections and also serious diseases, and its increasing antibiotic resistance necessitates further discovery of new targets and inhibitors for antibacterials. The transmembrane protein LcpASA that plays an essential role in the synthesis of cell wall in S. aureus has been identified as a potential drug target. In this study, we performed virtual screening of chemical compound libraries to establish their binding with target protein and molecular docking among other studies which led to identification of hit compounds with good binding affinity towards LcpASA domain and involvement of key amino acid residues in the intermolecular interactions. All molecules showed satisfactory drug-likeness properties such as ADME and non-carcinogenicity. 500 ns molecular dynamics (MD) simulations using Amber18 was performed on all molecular systems to explain the mechanism of LcpASA extracellular domain function and reveal potential hit molecules to bind the enzyme. Based on the post-MD data analysis; such as RMSD, RMSF, SASA, intermolecular hydrogen bonds, clustering analysis, anisotropic network model-based normal mode analysis and mechanical stiffness, and essential dynamics seven molecules were finally selected as hit compounds to bind LcpASA. Steered MD was employed to study the unbinding of the hit molecules.

Background: In the US, 120,000 cases of Staphylococcus aureus bacteremia (SAB) occur annually. Apart from mortality, little is known about other unfavorable outcomes (UOs). We developed a multifaceted definition for UOs in SAB and examined their incidence and predictors. Methods: We conducted a multicenter (~300 hospitals) retrospective cohort study between 2020 and 2022 of adult hospitalized patients with at least one blood culture (BC) positive for S. aureus. UOs were any of the following: hospital mortality, antibiotic escalation, persistently positive BCs, prolonged post-infection length of stay (LOS), 30-day readmission, and disease worsening. We compared the group with UOs to favorable outcomes (FOs). Regression models identified predictors of UOs. Results: Among 4080 patients with SAB, 2427 (59.5%) experienced a UO, most commonly 30-day readmission (42.0%) and antibiotic escalation (37.7%). Those with UOs more frequently had septic shock at admission (5.7% vs. 1.2%), requiring the ICU (18.8% vs. 14.7%) and dialysis (4.4% vs. 1.9%) prior to SAB onset. Community-onset SAB predominated in both groups, with more complicated SAB in the UO group (39.8% vs. 22.3%). Vancomycin use was similar, while daptomycin was more common in the UO group (8.5% vs. 3.0%). Variables with the highest odds ratios predicting a UO were septic shock on admission (3.498, 95% CI 2.145, 5.704), empiric daptomycin (2.723, 95% CI 1.943, 3.821), and complicated SAB (2.476, 95% CI 2.047, 2.994). Conclusions: UOs occur frequently in the setting of SAB. A broader perspective exploring issues other than mortality demonstrates the substantial implications of SAB both for patients and healthcare systems. Select clinical variables are associated with UOs, some of which may not be modifiable.

Staphylococcus aureus (S. aureus) infection is a serious threat to global health. This study aimed to investigate the anti-virulence efficacy of tigecycline against S. aureus. We used highly virulent S. aureus strains SA75 and JP30 to evaluate the effect of tigecycline on virulence, both of them isolated from the clinic. The MIC value of tigecycline against SA75 was 0.125 µg/mL, and that against JP30 was 0.25 µg/mL. Tigecycline did not affect the growth ability of bacteria at 0.015 µg/mL. Thus, subsequent discussions will focus on the effect of antibiotics at the latter subinhibitory concentrations that did not affect growth. First, the sub-MICs of tigecycline not only enhanced the sensitivity of S. aureus to oxidants and human whole blood but also weakened the hemolytic activity and cell adhesion level of S. aureus. Second, it undermined the survival of S. aureus in RAW264.7 and attenuated the macrophage inflammatory response induced by S. aureus. On the contrary, tigecycline decreased the hemolytic activity, as well as the skin abscess formation and bacterial burden in mice. Most importantly, it significantly decreased the expression of hla, hlgB, hlgC, spa, sbi, saeR, sak, tst, and coa genes by RT-qPCR and the protein expression of α-toxin. Altogether, the sub-MICs of tigecycline might be a promising agent to attenuate the virulence of S. aureus and its host immune response by inhibiting the SaeRS two-component system and the product of α-toxin.IMPORTANCEIn this study, the sub-MICs of tigecycline decreased the resistance of S. aureus to oxidants and human whole blood. Moreover, tigecycline weakened the cell adhesion level of S. aureus and skin abscess formation in mice by reducing bacterial burden. Remarkably, tigecycline decreased the hemolytic activity and significantly downregulated the expression of various virulence genes and α-toxin. This research highlighted that the sub-MICs of tigecycline might be a promising agent to attenuate the virulence of S. aureus by inhibiting the product of α-toxin.

Antibiotics represent one of the most significant medical breakthroughs of the twentieth century, playing a critical role in combating bacterial infections. However, the rapid emergence of antibiotic resistance has become a major global health crisis, significantly complicating treatment protocols. This paper provides a narrative review of the current state of antibiotic resistance, synthesizing findings from primary research and comprehensive review articles to examine the various mechanisms bacteria employ to counteract antibiotics. One of the primary sources of antibiotic resistance is the improper use of antibiotics in the livestock industry. The emergence of drug-resistant microorganisms from human activities and industrial livestock production has presented significant environmental and public health concerns. Today, resistant nosocomial infections occur following long-term hospitalization of patients, causing the death of many people, so there is an urgent need for alternative treatments. In response to this crisis, non-antibiotic therapeutic strategies have been proposed, including bacteriophages, probiotics, postbiotics, synbiotics, fecal microbiota transplantation (FMT), nanoparticles (NPs), antimicrobial peptides (AMPs), antibodies, traditional medicines, and the toxin-antitoxin (TA) system. While these approaches offer innovative solutions for addressing bacterial infections and preserving the efficacy of antimicrobial therapies, challenges such as safety, cost-effectiveness, regulatory hurdles, and large-scale implementation remain. This review examines the potential and limitations of these strategies, offering a balanced perspective on their role in managing bacterial infections and mitigating the broader impact of antibiotic resistance.

Methicillin-resistant Staphylococcus aureus (MRSA) are resistant to nearly all β-lactam antibiotics under standard testing conditions. However, a novel phenotype exists wherein certain MRSA strains exhibit β-lactam susceptibility in the presence of bicarbonate (termed 'NaHCO3-responsive'), an abundant ion in mammalian tissues and blood. This suggests that specific MRSA infections may be treatable by β-lactams. NaHCO3 responsiveness appears due to effects of NaHCO3 on the expression mecA/PBP2a and other accessory genes required for PBP functionality. mecA expression can be co-regulated by the bla operon regulatory genes, blaI and blaR1.

To elucidate the influence of NaHCO3 specifically on the bla operon via investigations of the impact of NaHCO3 on β-lactamase hyper-producing, mecA-negative, borderline oxacillin-resistant Staphylococcus aureus (BORSA) strains.

Evaluate the effect of NaHCO3 on β-lactam susceptibility via minimum inhibitory concentrations (MIC) assay, expression of genes within the bla operon (blaZ, blaI, blaR1) via RT-qPCR, and β-lactamase (BlaZ) activity via nitrocefinase assay in BORSA.

NaHCO3 enhanced susceptibility to β-lactamase-susceptible β-lactams penicillin and ampicillin. NaHCO3 had no impact on susceptibility to the anti-staphylococcal β-lactams oxacillin and cefazolin, or the anti-MRSA antibiotics vancomycin and daptomycin. NaHCO3 repressed expression of all genes within the bla operon and reduced β-lactamase production.

These data demonstrate that NaHCO3 influences expression of genes within the bla operon, translating to reduced β-lactamase production and enhanced β-lactam susceptibility in BORSA strains. Furthermore, this indicates that the classical blaZ regulators, blaI and blaR1, are the likely mediators of NaHCO3-mediated repression of mecA. However, questions still remain regarding the mechanism via which NaHCO3 regulates the bla operon.

Biological ageing, healthcare interactions, and pharmaceutical and environmental exposures in later life alter the characteristics of the oropharyngeal (OP) microbiome. These changes, including an increased susceptibility to colonisation by pathobiont species, have been linked with diverse health outcomes.

To investigate the relationship between OP microbiome characteristics and all-cause mortality in long-term aged care residents.

OP swabs were collected from 190 residents of five aged care facilities in South Australia. Microbiota composition was assessed by shotgun metagenomics and related to health outcomes during a 12-month follow-up period. OP carriage of Staphylococcus aureus and methicillin resistance was confirmed by qPCR.

OP carriage of S. aureus was identified in 13 (6.8%) residents. Detection of S. aureus was significantly associated with an increased risk of mortality (adjusted HR [95% CI]: 9.7 [3.8-24.9], P < .0001), compared with non-carriers, independent of methicillin resistance. Staphylococcus aureus carriage demonstrated a stronger association with mortality risk than the total number of comorbidities at the univariate level (S. aureus HR [95% CI]: 7.2 [3.4-15.5], P < .0001 vs. comorbidity count HR [95% CI]: 1.1 [1.0-1.3], P = .03), and remained significant after multivariable adjustment. Staphylococcus aureus detection was significantly associated with total number of comorbidities (adjusted OR [95% CI]: 1.4 [1.0-2.0], P = .04).

OP S. aureus carriage predicts all-cause mortality in long-term aged care. We speculate that S. aureus carriage represents a marker of general health, including prior healthcare exposures. OP S. aureus carriage could contribute to estimations of general health in older individuals and thereby inform care strategies.

Penicillin-binding protein 4 (PBP4) is essential in imparting significant β-lactam antibiotics resistance in Staphylococcus aureus (S. aureus) and the mutation R200L in PBP4 is linked to β-lactam non-susceptibility in natural strains, complicating treatment options. Therefore, discovering novel therapeutics against the mutant PBP4 is crucial, and natural compounds from lichen have found relevance in this regard. The aim of our study was to identify novel inhibitors against the R200L mutation by applying machine learning (ML) approach. Predictive classification models were developed using six machine learning algorithms to categorize lichen-derived compounds as either active or inactive. The models were evaluated using ROC curves, confusion matrices, and relevant statistical parameters. Among these, the Extra Trees algorithm showed superior predictive accuracy at 81%. The model identified 115 potentially active compounds from lichen, which were further evaluated for drug-likeness and structural similarity to β-lactam antibiotics. The top 23 compounds, showing similarity to β-lactam drug, were subjected to molecular docking. Among the top 10 compounds, two compounds, Barbatolic acid and Orcinyl lecanorate, displayed promising results in 200 ns molecular dynamics (MD) simulations and MM-PBSA analysis, exhibiting better docking score compare to reference compound. Additionally, DFT calculations revealed negative binding energies and smaller HOMO-LUMO gaps for both compounds. The obtained results prove the utility of ML in screening natural compounds, and provide novel opportunities for the design of antimicrobial compounds in the future.

The emergence of antibiotic-resistant strains caused by the extensive use of antibiotics in the world requires a preventive approach to stop the infection spread, especially in a hospital setting. So, there is a growing demand for materials that can inhibit bacteria growth or have bactericidal effects. In this paper, an inexpensive and durable Cu-containing strontium-modified phosphate glass with a considerable antimicrobial effect is proposed. The basic physical properties of the material are studied, and its antimicrobial effect is evaluated on Staphylococcus aureus bacteria, known to be the most common problem in hospital environments because of healthcare-associated infections. The glass powders demonstrate strong antibacterial efficacy with a concentration of only a few mg/mL, sufficient to eradicate the entire bacterial colonies within 24 h. Bulk surfaces of these glasses inhibit bacterial growth and release low, non-toxic levels of their constituent elements into simulated body fluid. On the basis of the obtained results, it is shown that the proposed glass can be used as a structural material for various medical equipment and/or components of antimicrobial coating/paint not only in medicine but also for high touch point articles in public places like schools, gyms, public offices and similar.

Staphylococcus aureus is one of the most common pathogens that colonizes human skin/mucous membranes, where it causes local infection that can progress to invasive infection, resulting in high morbidity and mortality worldwide. This study aimed to investigate the antibiotic susceptibility and molecular characteristics of invasive S. aureus in children and women in Southwest China from 2018 to 2023 to provide novel insights helpful in preventing and treating S. aureus infections.

The demographic and clinical characteristics of patients with invasive S. aureus infection were collected and analyzed. Next-generation sequencing (NGS) and sequence analysis techniques were used to determine the molecular epidemiological characteristics of the S. aureus isolates, and the microdilution broth method was used for antimicrobial susceptibility testing.

A total of 108 invasive S. aureus isolates, 29 methicillin-resistant S. aureus (MRSA) isolates and 79 methicillin- susceptible S. aureus (MSSA) isolates, were included. The isolates had the highest rate of resistance to PEN, at 91.67%, with all the MRSA isolates being resistant; the next highest resistance was to ERY and CLI, both at 65.74%. A total of 32 STs (including 8 novel STs) were detected and divided into 10 CCs. Moreover, 45 spa types were also detected. The main STs were ST22 (17.59%) and ST59 (15.74%), and the main CCs were CC59 (21.30%) and CC22 (19.44%). The most prevalent spa types were t309 and t437, both at 14.81%, and the SCCmec type could be assigned to two categories: IV (62.07%) and V (34.48%). Among the 29 MRSA isolates tested, CC59-IV-t437 (34.48%) and CC59-V-t437 (13.79%) were the main lineages, and among the 79 MSSA isolates, CC22-t309 (18.99%), CC1-t189 (10.13%), and CC5-t002 (7.60%) were the main lineages. Except for SXT, the resistance rates of the 29 MRSA isolates were greater than those of the MSSA isolates. Most isolates carried common virulence genes, among which the carriage rate of pvl reached 33.33%.

This study provides valuable information, including the prevalence, molecular characteristics and antimicrobial resistance of S. aureus isolates that cause invasive infectious diseases in Southwest China, and the findings may advance the prevention and treatment of S. aureus infections.

Staphylococcus aureus (S. aureus) is a prominent infectious etiological agent in humans, dairy animals, and camels. Camel milk has all the nutrients which are nutritious and advantageous to the growth of S. aureus that dominates most bacterial species. So, the present work was designed to investigate the effect of certain toxin gene of S. aureus bacteria isolated from raw camel milk on the fine structure of mice kidneys. Two toxin genes of S. aureus were identified and described through PCR using 23s rRNA primer for 23s rRNA gene. In addition, the effect of the isolated S. aureus bacteria, especially those carrying the gene "tst" was studied on the ultrastructure of mice kidney. Twenty male albino mice were allocated into 2 groups, control group and infected group (orally administered with a single dosage of S. aureus aqueous solutions from camel milk at a concentration of 5 × 108 colony forming unit/0.1 mL for three days). Infection of mice with S. aureus resulted in vacuolation, necrosis, and degeneration of tubular epithelial cells, intertubular congestion and inflammation, as well as dilatation and congestion of glomeruli. Therefore, this current study most likely indicates that camel milk infected with S. aureus has a significant and clear impact in inducing symptoms of kidney failure in communities that use these dairy products without health supervision, especially nomadic and pastoral communities.

Based on the inhibitory potencies from earlier reported tetrazole thioether analogs, we now describe the synthesis and inhibition of pyrazole-based inhibitors of N-succinyl-l,l-2,6-diaminopimelic acid desuccinylase (DapE) from Haemophilus influenzae (HiDapE). The most potent pyrazole analog 7d bears an aminopyridine amide with an IC50 of 17.9 ± 8.0 μM, and the single enantiomer of ɑ-methyl analog 7q has an IC50 of 18.8 µM, with potency residing in the (R)-enantiomer. Thermal shift revealed strong stabilization upon binding inhibitor (R)-7q with Tm = 50.2 °C and a Ki of 17.3 ± 2.8 μM. Enzyme kinetic experiments confirm competitive inhibition, and docking reveals key active site interactions.

The infestation of tissue after implantation is a major problem as a bacterial biofilm can form on the surface of the implants, leading to implant-associated infections (IAIs). One approach to prevent such IAI is to apply antibacterial coatings consisting of polyelectrolyte multilayers (PEM) and bacteriophages (PHAGs). PEM were constructed by alternately adsorbing oppositely charged polyelectrolytes on a substrate according to the layer-by-layer concept. Poly(ethylenimine) (PEI) was used as the cationic polyelectrolyte, and a graft polymer of hyaluronic acid and poly(l-lactide) (DAC) was used as the anionic polyelectrolyte. Comparing PEM-5 (PEI/DAC/PEI/DAC/PEI) and PEM-6 (PEI/DAC/PEI/DAC/PEI/DAC), a higher amount of PHAG was bound to PEM-5 with cationic surface charge, which was detected by atomic force microscopy (AFM) measurements and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The binding of PHAG to the PEM is suggested to be based on electrostatic interactions between the anionic capsid proteins of PHAG and the outermost PEM surface. For antibacterial tests, PEM-5 and PEM-6 each with and without contact to PHAG were deposited at agar plates and infected with bacteria. For the coatings consisting of PEM and PHAG, a significant eradicative effect toward bacteria was obtained, while the pure PEM coatings showed no eradication, which proves the dominant antibacterial contribution originated by PHAG.

Gram-positive bacteria utilize a Fatty Acid Kinase (FAK) complex to harvest fatty acids from the environment. This complex consists of the fatty acid kinase, FakA, and an acyl carrier protein, FakB, and is known to impact virulence and disease outcomes. Despite some recent studies, there remain many outstanding questions as to the enzymatic mechanism and structure of FAK. To better address this knowledge gap, we used a combination of modeling, biochemical, and cell-based approaches to build on prior proposed models and identify critical details of FAK activity. Using bio-layer interferometry, we demonstrated nanomolar affinity between FakA and FakB which also indicates that FakA is dimer when binding FakB. Additionally, targeted mutagenesis of the FakA Middle domain demonstrates it possesses a metal binding pocket that is critical for FakA dimer stability and FAK function in vitro and in vivo. Lastly, we solved structures of the apo and ligand-bound FakA kinase domain to capture the molecular changes in the protein following ATP binding and hydrolysis. Together, these data provide critical insight into the structure and function of the FAK complex which is essential for understanding its mechanism.

Staphylococcus aureus is a Gram-positive, opportunistic human pathogen that is a leading cause of skin and soft tissue infections and invasive disease worldwide. Virulence in this bacterium is tightly controlled by a network of regulatory factors. One such factor is the global regulatory protein CodY. CodY links branched-chain amino acid sufficiency to the production of surface-associated and secreted factors that facilitate immune evasion and subversion. Our previous work revealed that CodY regulates virulence factor gene expression indirectly in part by controlling the activity of the SaeRS two-component system (TCS). While this is correlated with an increase in membrane anteiso-15:0 and -17:0 branched-chain fatty acids (BCFAs) derived from isoleucine, the true mechanism of control has remained elusive. Herein, we report that CodY-dependent regulation of SaeS sensor kinase activity requires BCFA synthesis. During periods of nutrient sufficiency, BCFA synthesis and Sae TCS activity are kept relatively low by CodY-dependent repression of the ilv-leu operon and the isoleucine-specific permease gene brnQ2. In a codY null mutant, which simulates extreme nutrient limitation, de-repression of ilv-leu and brnQ2 directs the synthesis of enzymes in redundant de novo and import pathways to upregulate production of BCFA precursors. Overexpression of brnQ2, independent of CodY, is sufficient to increase membrane anteiso BCFAs, Sae-dependent promoter activity, and SaeR ~P levels. Our results further clarify the molecular mechanisms by which CodY controls virulence in S. aureus.IMPORTANCEExpression of bacterial virulence genes often correlates with the exhaustion of nutrients, but how the signaling of nutrient availability and the resulting physiological responses are coordinated is unclear. In S. aureus, CodY controls the activity of two major regulators of virulence-the Agr and Sae two-component systems (TCSs)-by unknown mechanisms. This work identifies a mechanism by which CodY controls the activity of the sensor kinase SaeS by modulating the levels of anteiso branched-chain amino acids that are incorporated into the membrane. Understanding the mechanism adds to our understanding of how bacterial physiology and metabolism are linked to virulence and underscores the role virulence in maintaining homeostasis. Understanding the mechanism also opens potential avenues for targeted therapeutic strategies against S. aureus infections.

The use of matrix-assisted laser desorption/ionisation-time-of-flight mass spectra (MALDI-TOF MS) with machine learning (ML) has been explored for predicting antimicrobial resistance. This study evaluates the effectiveness of MALDI-TOF MS paired with various ML classifiers and establishes optimal models for predicting antimicrobial resistance and the presence of mecA gene among Staphylococcus aureus.

Antimicrobial resistance against tier 1 antibiotics and MALDI-TOF MS of S. aureus were analysed using data from the Database of Resistance against Antimicrobials with MALDI-TOF Mass Spectrometry (DRIAMS) and one medical centre (CS database). Five ML classifiers were used to analyse performance metrics. The Shapley value quantified the predictive contribution of individual features.

The LightGBM demonstrated superior performance in predicting antimicrobial resistance for most tier 1 antibiotics among oxacillin-resistant S. aureus (ORSA) compared with all S. aureus and oxacillin-susceptible S. aureus (OSSA) in both databases. In DRIAMS, Multilayer Perceptron (MLP) was associated with excellent predictive performance, expressed as accuracy/AUROC/AUPR, for clindamycin (0.74/0.81/0.90), tetracycline (0.86/0.87/0.94), and trimethoprim-sulfamethoxazole (0.95/0.72/0.97). In the CS database, Ada and Light Gradient Boosting Machine (LightGBM) showed excellent performance for erythromycin (0.97/0.92/0.86) and tetracycline (0.68/0.79/0.86). Mass-to-charge ratio (m/z) features of 2411-2414 and 2429-2432 correlated with clindamycin resistance, whereas 5033-5036 was linked to erythromycin resistance in DRIAMS. In the CS database, overlapping features of 2423-2426, 4496-4499, and 3764-3767 simultaneously predicted the presence of mecA and oxacillin resistance.

The predictive performance of antimicrobial resistance against S. aureus using MALDI-TOF MS depends on database characteristics and the ML algorithm selected. Specific and overlapping mass spectra features are excellent predictive markers for mecA and specific antimicrobial resistance.

Staphylococcus aureus is a leading cause of pediatric bacteremia. Persistent S. aureus bacteremia (SAB) is associated with increased morbidity and mortality in adults and children. Risk factors for S. aureus bacteremia have been well established, but there is a limited understanding of the factors that contribute to the development of persistent SAB in children.

This is a single-center retrospective secondary analysis of a prospective observational study of pediatric patients hospitalized with S. aureus infection over a 3.5-year period at a large, quaternary, children's hospital.

Two hundred fifty-nine children with confirmed S. aureus infection were enrolled in the study. Sixty-five of these were found to have bacteremia, with 28 (43%) developing persistent bacteremia. Patients with persistent SAB were culture-positive for a median of 3.5 days compared with 1 day for those without ( P ≤ 0.001). Children with persistent SAB were more likely to have an identified osteoarticular source of infection (93%, n = 26 vs. 62%, n = 23; P = 0.008) and had a shorter median duration to culture positivity than those without persistent SAB (16 hours vs. 20 hours; P ≤ 0.001). In addition, children with persistent SAB had higher median values of presenting erythrocyte sedimentation rate, peak erythrocyte sedimentation rate, presenting C-reactive protein and peak C-reactive protein. Not surprisingly, hospital length of stay was longer in children with persistent SAB compared with those without.

These findings suggest that a shorter time to culture positivity, osteoarticular infection, and higher presenting and peak values for select inflammatory markers are potential risk factors for persistent SAB in children.

Wound infections, marked by the proliferation of microorganisms at surgical sites, necessitate the development of innovative wound dressings with potent bactericidal properties to curb microbial growth and prevent bacterial infiltration. This study explores the recent strides in utilizing ionic liquid-based polymers as highly promising antimicrobial agents for advanced wound healing applications. Specifically, cationic polymers containing quaternary ammonium, imidazolium, guanidinium, pyridinium, triazolium, or phosphonium groups have emerged as exceptionally effective antimicrobial compounds. Their mechanism of action involves disrupting bacterial membranes, thereby preventing the development of resistance and minimizing toxicity to mammalian cells. This comprehensive review not only elucidates the intricate dynamics of the skin's immune response and the various stages of wound healing but also delves into the synthesis methodologies of ionic liquid-based polymers. By spotlighting the practical applications of antimicrobial wound dressings, particularly those incorporating ionic liquid-based materials, this review aims to lay the groundwork for future research endeavors in this burgeoning field. Through a nuanced examination of these advancements, this article seeks to contribute to the ongoing progress in developing cutting-edge wound healing platforms that can effectively address the challenges posed by microbial infections in surgical wounds.

Awareness of health disparities' impact on clinical outcomes is increasing. However, public health's ability to highlight these trends can be limited by data missingness, such as on race and ethnicity. To better understand race and ethnicity's impact, we compared all-cause 30-day mortality rates between non-Hispanic (NH) Black, NH White, and Hispanic/NH other racial and ethnic patients among cases of carbapenem-resistant Enterobacterales (CRE).

We performed data linkage using CRE statewide surveillance, Hospital Discharge Data System, and vital records data to obtain demographics and clinical outcomes on CRE cases in TN. We evaluated the association between race and ethnicity with all-cause 30-day mortality among CRE cases.

Among 2,804 reported CRE cases from 2015 to 2019, 65% (n = 1,832) were missing race and ethnicity; data linkage methods reduced missingness to 10% (n = 285). 22%, 74%, and 3% of cases were among NH Black, NH White, and Hispanic/NH other patients, respectively. Thirty-day all-cause mortality among NH Black patients was 5.7 per 100,000 population, 1.9 and 5.7 times higher than NH White and Hispanic/NH other patients. We observed that the risk of dying within 30 days of CRE diagnosis was 35% higher for NH Black compared to NH White patients; unmeasured confounders may be present (adjusted risk ratio 1.35; 95% CI 1.00, 1.83).

Data linkage effectively reduced missingness of race and ethnicity. Among those with CRE, NH Blacks may have an increased risk of all-cause 30-day mortality. Data missingness creates barriers in identifying health disparities; data linkage is one approach to overcome this challenge.

Spiders produce webs, which are still a largely unexplored source of antibacterial compounds, although the reports of its application in the medical field. Therefore, this study aims to present an integrative review of the antibacterial activity of spider webs. The research was conducted using Google Scholar, Scielo, Web of Science, PubMed, ScienceDirect, Medline EBSCO, LILACS, and Embase. The inclusion criteria were original articles written in English that studied the antibiotic properties of the web or isolated compounds tested. The studies were compared according to the spider species studied, the type of web, treatment of the sample, type of antimicrobial test, and the results obtained. Nine hundred and seventy-three publications were found, and after applying the inclusion and exclusion criteria, sixteen articles were selected. Bacterial inhibition was found in seven studies against various species of bacteria such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Salmonella Typhi, Bacillus megaterium, Listeria monocytogenes, Acinetobacter baumannii, Streptococcus pneumoniae, Pasteurella multocida, and Bacillus subtilis. Additionally, there was no apparent relationship between the proximity of the spider species evaluated in the studies and the presence or absence of activity. Methodological problems detected may affected the reproducibility and reliability of the results in some studies, such as the lack of description of the web or microorganism strain, as well as the absence of adequate controls and treatments to sterilize the sample. Spider webs can be a valuable source of antibiotics; however, more studies are needed to confirm the real activity of the web or components involved.

Pericardial empyema, a rare but often fatal condition, is frequently diagnosed postmortem. Staphylococcus aureus is the most common causative organism. This case involves a 73-year-old male with diabetes and hypothyroidism who presented with chills, fever, and a persistent skin infection. Cultures revealed Methicillin-resistant Staphylococcus aureus (MRSA), and he was treated with intravenous Vancomycin. On the third day, the patient experienced sudden chest pain, and examination revealed muffled heart sounds, jugular venous distension, sinus tachycardia, and diffuse ST elevation. Transthoracic echocardiography (TTE) showed a large pericardial effusion. An emergent pericardiocentesis was performed, followed by a pericardial window, but the patient later developed a clot, leading to the removal of 1000 ml of the bloody fluid. He subsequently became dyspneic and experienced pulseless electrical activity, resulting in death from cardiopulmonary collapse. MRSA was confirmed in the pericardial fluid. This case underscores the critical need for prompt diagnosis and treatment of pericardial empyema due to its high mortality risk and often ambiguous clinical presentation.

We used a multi-state model, which mitigates time-dependent bias, to estimate the mortality, length of stay (LOS), and costs of methicillin-resistant Staphylococcus aureus (MRSA) infections in Singapore.

We conducted a retrospective study in a hospital in Singapore from 2018 to 2022. Patients with MRSA infections were matched 1:1:3 to patients with MRSA colonization and patients without MRSA by age, gender, specialty, and intensive care admission, respectively. A multi-state model was used to derive excess LOS and mortality hazard ratios. The attributable cost of infections was estimated in 2022 Singapore dollars (SGDs) from the health care perspective.

We matched 536 patients with MRSA infections to 536 patients with MRSA colonization, and to 1608 patients without MRSA. The excess LOS due to MRSA infection was 2.11 (95% confidence interval [CI] 2.05-2.17) days compared with MRSA colonization and 3.75 (95% CI 3.69-3.80) days compared with no MRSA, which translated to an excess cost of SGD $1825 and SGD $3238, respectively. Of the different MRSA infection types, pneumonia had the highest mortality risk (hazard ratio 4.13; 95% CI 2.28-7.50) compared with patients without MRSA.

MRSA infections increased hospital LOS and health care costs in Singapore. Our estimates can inform future economic analyses of management strategies against MRSA.

The increasing threat from antibiotic-resistant bacteria has necessitated the development of novel methods to counter bacterial infections. In this context, the application of metallic nanoparticles (NPs), especially gold (Au) and silver (Ag), has emerged as a promising strategy due to their remarkable antibacterial properties. This review examines research published between 2006 and 2023, focusing on leading journals in nanotechnology, materials science, and biomedical research. The primary applications explored are the efficacy of Ag and Au NPs as antibacterial agents, their synthesis methods, morphological properties, and mechanisms of action. An extensive review of the literature on NPs synthesis, morphology, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and effectiveness against various Gram(+/-) bacteria confirms the antibacterial efficacy of Au and Ag NPs. The synthesis methods and characteristics of NPs, such as size, shape, and surface charge, are crucial in determining their antibacterial activity, as these factors influence their interactions with bacterial cells. Furthermore, this review underscores the urgent necessity of standardizing synthesis techniques, MICs, and reporting protocols to enhance the comparability and reproducibility of future studies. Standardization is essential for ensuring the reliability of research findings and accelerating the clinical application of NP-based antimicrobial approaches. This review aims to propel NP-based antimicrobial strategies by elucidating the properties that enhance the antibacterial activity of Ag and Au NPs. By highlighting their inhibitory effects against various bacterial strains and relatively low cytotoxicity, this work positions Ag and Au NPs as promising materials for developing antibacterial agents, making a significant contribution to global efforts to combat antibiotic-resistant pathogens.

Multi-drug resistant Staphylococcus aureus is one of the most common causes of nosocomial and community-acquired infections, with high morbidity and mortality. Treatment of such infections is particularly problematic; hence, it is complicated by antibiotic resistance, and there is currently no reliable vaccine. Furthermore, it is well known that S. aureus produces an exceptionally large number of virulence factors that worsen infection. Consequently, the urgent need for anti-virulent agents that inhibit biofilm formation and virulence factors has gained momentum. Therefore, we focused our attention on an already-approved antibiotic and explored whether changing the dosage would still result in the intended anti-virulence effect.

In the present study, we determined the antibiotic resistance patterns and the MICs of oxacillin against 70 MDR S. aureus isolates. We also investigated the effect of sub-MICs of oxacillin (at 1/4 and 1/8 MICs) on biofilm formation using the crystal violet assay, the phenol-sulphuric acid method, and confocal laser scanning microscopy (CLSM). We examined the effect of sub-MICs on virulence factors and bacterial morphology using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and electron microscopy, respectively. Moreover, we studied the effect of sub-MICs of oxacillin (OX) in-vivo using a wound infection model.

Oxacillin at 1/2 MIC showed a significant decrease in bacterial viability, while 1/4 and 1/8 MICs had negligible effects on treated bacterial isolates. Treatment of MDR isolates with 1/4 or 1/8 MICs of oxacillin significantly reduced biofilm formation (64% and 40%, respectively). The treated MDR S. aureus with sub-MICs of OX exhibited a dramatic reduction in several virulence factors, including protease, hemolysin, coagulase, and toxic shock syndrome toxin-1 (TSST-1) production. The sub-MICs of OX significantly decreased (P < 0.05) the gene expression of biofilm and virulence-associated genes such as agrA, icaA, coa, and tst. Furthermore, oxacillin at sub-MICs dramatically accelerated wound healing, according to the recorded scoring of histological parameters.

The treatment of MDR S. aureus with sub-MICs of oxacillin can help in combating the bacterial resistance and may be considered a promising approach to attenuating the severity of S. aureus infections due to the unique anti-biofilm and anti-virulence activities.

The passion fruit, Passiflora edulis, recognized for its rich nutritional properties, has long been used for its varied ethnobotanical applications. This study investigates the therapeutic potential of P. edulis var. Tainung No. 1 rind extracts by examining their polyphenolic content (TPC), total flavonoid content (TFC), anti-skin aging activities against key enzymes such as elastase, tyrosinase, and hyaluronidase, and their ability to inhibit bacterial growth, single-stranded DNA-binding protein (SSB), and their cytotoxic effects on oral carcinoma cells. The acetone extract from the rind exhibited the highest levels of TPC, TFC, anti-SSB, and antibacterial activities. The antibacterial effectiveness of the acetone-extracted rind was ranked as follows: Escherichia coli > Pseudomonas aeruginosa > Staphylococcus aureus. A titration curve for SSB inhibition showed an IC50 value of 313.2 μg/mL, indicating the potency of the acetone extract in inhibiting SSB. It also significantly reduced the activity of enzymes associated with skin aging, particularly tyrosinase, with a 54.5% inhibition at a concentration of 100 μg/mL. Gas chromatography-mass spectrometry (GC-MS) analysis tentatively identified several major bioactive compounds in the acetone extract, including stigmast-5-en-3-ol, vitamin E, palmitic acid, stigmasterol, linoleic acid, campesterol, and octadecanoic acid. Molecular docking studies suggested some of these compounds as potential inhibitors of tyrosinase and SSB. Furthermore, the extract demonstrated anticancer potential against Ca9-22 oral carcinoma cells by inhibiting cell survival, migration, and proliferation and inducing apoptosis. These results underscore the potential of P. edulis (Tainung No. 1) rind as a promising candidate for anti-skin aging, antibacterial, and anticancer applications, meriting further therapeutic investigation.

Equitable representation of members from historically marginalized groups is important in clinical trials, which inform standards of care. The goal of this study was to characterize the demographics and proportional subgroup reporting and representation of participants enrolled in randomized controlled trials (RCTs) of antibacterials used to treat Staphylococcus aureus infections.

We examined randomized controlled registrational and strategy trials published from 2000 to 2021 to determine the sex, race, and ethnicity of participants. Participant to incidence ratios (PIRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the disease population in each group. Underrepresentation was defined as a PIR < 0.8.

Of the 87 included studies, 82 (94.2%) reported participant sex, 69 (79.3%) reported participant race, and 20 (23.0%) included ethnicity data. Only 17 (19.5%) studies enrolled American Indian/Alaskan Native participants. Median PIRs indicated that Asian and Black participants were underrepresented in RCTs compared with the incidence of methicillin-resistant S. aureus infections in these subgroups. Underrepresentation of Black participants was associated with a larger study size, international sites, industry sponsorship, and phase 2/3 trials compared with phase 4 trials (P < .05 for each). Black participants had more than 4 times the odds of being underrepresented in phase 2/3 trials compared with phase 4 trials (odds ratio, 4.57; 95% confidence interval: 1.14-18.3).

Standardized reporting methods for race and ethnicity and efforts to increase recruitment of marginalized groups would help ensure equity, rigor, and generalizability in RCTs of antibacterial agents and reduce health inequities.

KKL-35 is a new oxadiazole compound with potent broad-spectrum antibacterial activity against a number of gram-positive and gram-negative bacteria. However, its influences on bacterial growth are unclear. This study is to investigate phenotypic changes of Staphylococcus aureus (SA) caused by KKL-35 and evaluate antibacterial activity of combinations of KKL-35 with 7 class of antibiotics available in medical facilities. KKL-35-treated SA showed significantly lower survival under stresses of NaCl and H2O2 than DMSO (21.03 ± 2.60% vs. 68.21 ± 5.31% for NaCl, 4.91 ± 3.14% vs. 74.78 ± 2.88% for H2O2). UV exposure significantly decreased survival of SA treated with KKL-35 than DMSO-treated ones (23.91 ± 0.71% vs. 55.45 ± 4.70% for 4.2 J/m2, 12.80 ± 1.03% vs. 31.99 ± 5.99% for 7.0 J/m2, 1.52 ± 0.63% vs. 6.49 ± 0.51% for 14.0 J/m2). KKL-35 significantly decreased biofilm formation (0.47 ± 0.12 vs. 1.45 ± 0.21) and bacterial survival in the serum resistance assay (42.27 ± 2.77% vs. 78.31 ± 5.64%) than DMSO. KKL-35 significantly decreased ethidium bromide uptake and efflux, as well as the cell membrane integrity. KKL-35 had low cytotoxicity and low propensity for resistance. KKL-35 inhibited SA growth in concentration-independent and time-dependent manners, and showed additivity when combined with the majority class of available antibiotics. Antibiotic combinations of KKL-35 with ciprofloxacin, rifampicin, or linezolid significantly decreased bacterial loads than the most active antibiotic in the corresponding combination. Thus, KKL-35 inhibits growth of SA by decreasing bacterial environmental adaptations, biofilm formation, membrane uptake and efflux, as well as increasing antibiotic sensitivity. Its potent antibacterial activity, low cytotoxicity, low propensity for resistance, and wide choices in antibiotic combinations make KKL-35 a promising leading compound to design new antibiotics in monotherapies and combination therapies to treat bacterial infections.

Retrospective Case-Control series.

The objective of this study is to define the overall postoperative rate of surgical site infection (SSI) in patients undergoing spine surgery and examine the effects of intrawound Vancomycin on postoperative infection rates.

Surgical site infections (SSI) account for 22% of all health care-associated infections. The use of intrawound Vancomycin in an attempt to reduce the incidence of postoperative SSI has not been sufficiently evaluated in the existing literature.

All spine surgeries (n=19,081) from our institution were reviewed from 2003 to 2013. All cases of verified SSI were identified from the database. Cases were then matched to controls in a 1:1 fashion based on age, gender, and date of surgery (+/-30 d). Patient demographics, comorbidities, estimated blood loss, duration of surgery, intrawound administration of Vancomycin, and smoking status were evaluated.

At total of 316 cases of SSI after spine surgery were identified, representing an infection rate of 1.7%. The mean follow-up for cases and controls was 31.5 and 41.6 months, respectively. OR for intrawound Vancomycin was 0.44 (95% CI 0.23-0.88, P =0.019). OR for BMI greater than 30 was 1.63 (95% CI 1.04-2.56, P =0.03).

In this large cohort of spine surgery patients, administration of intrawound Vancomycin was associated with a significant reduction in postoperative surgical site infections. Further studies are needed to determine appropriate dosing and application as well as long-term safety in spine surgery.

We conducted a molecular epidemiological study of Staphylococcus aureus using whole-genome sequence data and clinical data of isolates from nasal swabs of patients admitted to the intensive care unit (ICU) of Hiroshima University hospital. The relationship between isolate genotypes and virulence factors, particularly for isolates that caused infectious diseases during ICU admission was compared with those that did not. The nasal carriage rates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in patients admitted to the ICU were 7.0% and 20.1%, respectively. The carriage rate of community-acquired (CA)-MRSA was 2.3%, accounting for 32.8% of all MRSA isolates. Whole-genome sequencing analysis of the MRSA isolates indicated that most, including CA-MRSA and healthcare-associated (HA)-MRSA, belonged to clonal complex (CC) 8 [sequence type (ST) 8] and SCCmec type IV. Furthermore, results for three disease foci (pneumonia, skin and soft tissue infection, and deep abscess) and the assessment of virulence factor genes associated with disease conditions [bacteremia, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), and septic shock] suggested that nasal colonization of S. aureus clones could represent a risk for patients within the ICU. Particularly, MRSA/J and MSSA/J may be more likely to cause deep abscess infection; ST764 may cause ventilation-associated pneumonia, hospital-acquired pneumonia and subsequent bacteremia, and ARDS, and tst-1-positive isolates may cause DIC onset.IMPORTANCENasal colonization of MRSA in patients admitted to the intensive care unit (ICU) may predict the development of MRSA infections. However, no bacteriological data are available to perform risk assessments for Staphylococcus aureus infection onset. In this single-center 2-year genomic surveillance study, we analyzed all S. aureus isolates from nasal swabs of patients admitted to the ICU and those from the blood or lesions of in-patients who developed infectious diseases in the ICU. Furthermore, we identified the virulent clones responsible for causing infectious diseases in the ICU. Herein, we report several virulent clones present in the nares that are predictive of invasive infections. This information may facilitate the design of preemptive strategies to identify and eradicate virulent MRSA strains, reducing nosocomial infections within the ICU.