• Yersinia pestis
• Peptide-based screen
• nLC-MS/MS

• Yersinia pestis/isolation & purification
• Tandem Mass Spectrometry/methods
• Peptides/analysis
• Peptides/chemistry
• Chromatography, Liquid/methods
• Bacterial Proteins/analysis
• Proteomics/methods
• Plague/microbiology
• Soil Microbiology
• Proteome/analysis
• Humans

• Control
• Cross-contamination
• Foodborne bacteria
• Molecular subtyping
• Persistent bacteria
• Pork meat
• Prevention

• Animals
• Swine
• Foodborne Diseases/microbiology
• Foodborne Diseases/prevention & control
• Food Microbiology
• Humans
• Pork Meat/microbiology
• Food Contamination
• Bacteria/isolation & purification
• Bacteria/classification
• Red Meat/microbiology
• Yersinia enterocolitica/isolation & purification
• Listeria monocytogenes/isolation & purification

• MgtC
• Yersinia pseudotuberculosis
• intracellular survival
• pathogenic

• 2023-YWF-ZYSQ-05 Central Public-Interest Scientific Institution Basal Research Fund of Institute of Animal Science of Chinese Academy of Agricultural Sciences
• cxgc-ias-15 The Agricultural Science and Technology Innovation Program of China

• Far East scarlet-like fever
• Yersinia pseudotuberculosis
• genome

• Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche
• AID-DGA French Ministry of Armed Forces | Agence de l'innovation de Défense (AID)
• FDT202204015222 Fondation pour la Recherche Médicale (FRM)
• ANR-16-CONV-0005 Inception program

• Yersinia
• host-pathogen interactions
• human innate immunity
• inflammasome
• intestinal epithelial cell
• macrophages

• Humans
• Animals
• Mice
• Yersinia
• Inflammasomes
• Yersinia pestis
• Yersinia pseudotuberculosis
• Plague

• R21 AI151476 NIAID NIH HHS
• R01 AI139102 NIAID NIH HHS
• R01 AI128530 NIAID NIH HHS
• R01 AI118861 NIAID NIH HHS
• T32 AI141393 NIAID NIH HHS
• R01 AI123243 NIAID NIH HHS
• R21 AI163596 NIAID NIH HHS
• HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)

• R21 AI151476 NIAID NIH HHS
• R01 AI139102 NIAID NIH HHS
• R01 AI118861 NIAID NIH HHS
• T32 AI141393 NIAID NIH HHS
• R01 AI123243 NIAID NIH HHS
• R21 AI163596 NIAID NIH HHS

• Plasmid copy number
• Plasmid replication
• T3SS
• Yersinia

• RNA-Seq
• Yersinia
• database
• genome
• mass spectrometry
• microarray
• multi-omics
• proteome
• synteny
• transcriptome

• Institut Pasteur
• Centre National de la Recherche Scientifique (CNRS)
• French Ministry of Defense | Direction Générale de l'Armement (DGA)
• Agence Nationale de la Recherche (ANR)
• Fondation pour la Recherche Médicale (FRM)
• Université de Paris (University of Paris)
• Université Côte d'Azur (UCA)

• bacterial pathogenesis
• host-pathogen interactions
• phospho-proteome
• phosphorylation
• post-translational modifications
• secretion systems
• signal transduction

• Pore-forming protein
• Protein secretion
• Translocon
• Transmembrane protein
• Type-III-Secretion

• Gram-negative bacterial pathogens
• artificial intelligence
• effector network
• network robustness
• type III secretion system effectors

• Citrobacter rodentium/genetics
• Enterohemorrhagic Escherichia coli/genetics
• Escherichia coli Proteins/metabolism
• Salmonella enterica/metabolism
• Type III Secretion Systems/genetics
• Type III Secretion Systems/metabolism
• Virulence Factors/genetics
• Virulence Factors/metabolism

• MR/R020671/1 Medical Research Council

• M cell
• Yersinia pseudotuberculosis
• YopE
• YopH
• cell extrusion
• human ileal enteroid
• organoid
• polarized epithelial
• transcytosis
• type three secretion system

• PGPR
• Pseudomonas
• biocontrol
• mycorrhization
• nodulation
• plant immunity
• protists
• rhizobia
• rhizosphere
• type III secretion system

• None Natural Sciences and Engineering Research Council

To identify sequences with a role in microbial pathogenesis, we assessed the adequacy of their annotation by existing controlled vocabularies and sequence databases. Our goal was to regularize descriptions of microbial pathogenesis for improved integration with bioinformatic applications. Here, we review the challenges of annotating sequences for pathogenic activity. We relate the categorization of more than 2,750 sequences of pathogenic microbes through a controlled vocabulary called Functions of Sequences of Concern (FunSoCs). These allow for an ease of description by both humans and machines. We provide a subset of 220 fully annotated sequences in the supplemental material as examples. The use of this compact (∼30 terms), controlled vocabulary has potential benefits for research in microbial genomics, public health, biosecurity, biosurveillance, and the characterization of new and emerging pathogens.

• Function identification
• Pearl gentian grouper
• Type Ⅲ secretion system
• Vibrio harveyi
• vscCD

• Animals
• Fish Diseases
• Hydrogen Peroxide
• Type III Secretion Systems/genetics
• Vibrio/genetics
• Vibrio Infections/veterinary

The type III secretion system (T3SS) is a virulence apparatus used by many Gram-negative pathogenic bacteria to cause infections. Pathogens utilizing a T3SS are responsible for millions of infections yearly. Since many T3SS knockout strains are incapable of causing systemic infection, the T3SS has emerged as an attractive anti-virulence target for therapeutic design. The T3SS is a multiprotein molecular syringe that enables pathogens to inject effector proteins into host cells. These effectors modify host cell mechanisms in a variety of ways beneficial to the pathogen. Due to the T3SS’s complex nature, there are numerous ways in which it can be targeted. This review will be focused on the direct targeting of components of the T3SS, including the needle, translocon, basal body, sorting platform, and effector proteins. Inhibitors will be considered a direct inhibitor if they have a binding partner that is a T3SS component, regardless of the inhibitory effect being structural or functional.

• anti-virulence
• antibacterials
• inhibition
• type III secretion system

• Adenosine Triphosphatases/chemistry
• Animals
• Anti-Bacterial Agents/pharmacology
• Bacterial Outer Membrane Proteins/genetics
• Bacterial Proteins/genetics
• Cytoplasm/metabolism
• Genomic Islands
• Gram-Negative Bacteria/genetics
• Humans
• Molecular Chaperones/chemistry
• Peptides/chemistry
• Periplasm/metabolism
• Protein Binding
• Protein Domains
• Protein Transport
• Salmonella
• Type III Secretion Systems/metabolism
• Virulence

• UL1 TR002649 NCATS NIH HHS

• Y. pestis
• Y. pseudotuberculosis
• Y. ruckeri
• Yersinia enterocolitica
• autophagy
• enteric yersiniosis
• plague

• Humans
• Autophagy
• Animals
• Intracellular Membranes/metabolism
• Host-Pathogen Interactions
• Yersinia/metabolism
• Yersinia/pathogenicity
• Yersinia pseudotuberculosis/metabolism
• Yersinia pseudotuberculosis/pathogenicity
• Yersinia Infections/microbiology
• Yersinia Infections/metabolism
• Yersinia enterocolitica/metabolism
• Yersinia enterocolitica/pathogenicity

• Yersinia Research Unit Institut Pasteur
• MENESR 511 Ministère Français de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche
• ANR-15-CE15-0017 Agence Nationale de la Recherche
• ANR-LBX-62-IBEID LabEx IBEID

• Yersinia pestis
• affinities
• avidities
• binding sites
• monoclonal antibodies
• passive protection
• plague

Integration of genetic networks allows bacteria to rapidly adapt to changing environments. This is particularly important in bacteria that interact with multiple hosts. Erwinia carotovora is a plant pathogen that uses Drosophila melanogaster as a vector. To interact with these two hosts, Ecc15 uses different sets of virulence factors: plant cell wall-degrading enzymes to infect plants and the Erwinia virulence factor (evf) to infect Drosophila. Our work shows that, despite the virulence factors being specific for each host, both sets are coactivated by homoserine lactone quorum sensing and by the two-component GacS/A system in infected plants. This regulation is essential for Ecc15 loads in the gut of Drosophila and minimizes the developmental delay caused by the bacteria with respect to the insect vector. Our findings provide evidence that coactivation of the host-specific factors in the plant may function as a predictive mechanism to maximize the probability of transit of the bacteria between hosts.

Multihost bacteria have to rapidly adapt to drastic environmental changes, relying on a fine integration of multiple stimuli for an optimal genetic response. Erwinia carotovora spp. are phytopathogens that cause soft-rot disease. Strain Ecc15 in particular is a model for bacterial oral-route infection in Drosophila melanogaster as it harbors a unique gene, evf, that encodes the Erwinia virulence factor (Evf), which is a major determinant for infection of the D. melanogaster gut. However, the factors involved in the regulation of evf expression are poorly understood. We investigated whether evf could be controlled by quorum sensing as, in the Erwinia genus, quorum sensing regulates pectolytic enzymes, the major virulence factors needed to infect plants. Here, we show that transcription of evf is positively regulated by quorum sensing in Ecc15 via acyl-homoserine lactone (AHL) signal synthase ExpI and AHL receptors ExpR1 and ExpR2. We also show that the load of Ecc15 in the gut depends upon the quorum sensing-mediated regulation of evf. Furthermore, we demonstrate that larvae infected with Ecc15 suffer a developmental delay as a direct consequence of the regulation of evf via quorum sensing. Finally, we demonstrate that evf is coexpressed with plant cell wall-degrading enzymes (PCWDE) during plant infection in a quorum sensing-dependent manner. Overall, our results show that Ecc15 relies on quorum sensing to control production of both pectolytic enzymes and Evf. This regulation influences the interaction of Ecc15 with its two known hosts, indicating that quorum sensing signaling may impact bacterial dissemination via insect vectors that feed on rotting plants.

• Drosophila
• Ecc15
• bacterial infections
• homoserine lactones
• host-pathogen interactions
• insect development
• invertebrate-microbe interactions
• quorum sensing

• OmpR regulator
• Yersinia enterocolitica
• proteome
• strain-specific differences
• urease activity
• urease-subunits genes

Bacterial infections continue to threaten humankind and the rapid spread of antibiotic resistant bacteria is alarming. Current antibiotics target essential bacterial processes and thereby apply a strong selective pressure on pathogenic and non-pathogenic bacteria alike. One alternative strategy is to block bacterial virulence systems that are essential for the ability to cause disease but not for general bacterial viability. We have previously show that the plant natural product (-)-hopeaphenol blocks the type III secretion system (T3SS) in the Gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. (-)-Hopeaphenol is a resveratrol tetramer and in the present study we explore various resveratrol dimers, including partial structures of (-)-hopeaphenol, as T3SS inhibitors. To allow rapid and efficient assessment of T3SS inhibition in P. aeruginosa, we developed a new screening method by using a green fluorescent protein reporter under the control of the ExoS promoter. Using a panel of assays we showed that compounds with a benzofuran core structure i.e. viniferifuran, dehydroampelopsin B, anigopreissin A, dehydro-δ-viniferin and resveratrol-piceatannol hybrid displayed significant to moderate activities towards the T3SS in Y. pseudotuberculosis and P. aeruginosa.

Yersinia pestis, the etiological pathogen of plague, is capable of repressing the immune response of white blood cells to evade phagocytosis. The V-antigen (LcrV) was found to be involved in this process by binding to human Toll-like Receptor 2 (TLR2). The detailed mechanism behind this LcrV and TLR2 mediated immune response repression, however, is yet to be fully elucidated due to the lack of structural information.

In this work, with protein structure modelling, we were able to construct a structure model of the heterotetramer of Y. pestis LcrV and human TLR2. Molecular dynamics simulation suggests the stability of this structure in aquatic environment. The LcrV model has a dumbbell-like structure with two globule domains (G1 at N-terminus and G2 away from membrane) connected with a coiled-coil linker (CCL) domain. The two horseshoe-shape TLR2 subunits form a V-shape structure, are not in direct contact with each other, and are held together by the LcrV homodimer. In this structure model, both the G1 and CCL domains are involved in the formation of LcrV homodimer, while all three domains are involved in LcrV-TLR2 binding. A mechanistic model was proposed based on this heterotetrameric structure model: The LcrV homodimer separates the TLR2 subunits to inhibit the dimerization of TLR2 and subsequent signal transfer for immune response; while LcrV could also inhibit the formation of heterodimers of TLR2 with other TLRs, and leads to immune response repression.

A heterotetrameric structure of Y. pestis LcrV and human TLR2 was modelled in this work. Analysis of this modelled structure showed its stability in aquatic environments and the role of LcrV domains and residues in protein-protein interaction. A mechanistic model for the role of LcrV in Y. pestis pathogenesis is raised based on this heterotetrameric structure model. This work provides a hypothesis of LcrV function, with which further experimental validation may elucidate the role of LcrV in human immune response repression.

• Immune response repression
• LcrV
• Plague
• Structure modelling
• TLR2
• Toll-like receptor
• V-antigen
• Yersinia pestis

The Gram-negative bacterial envelope is an essential interface between the intracellular and harsh extracellular environment. Envelope stress responses (ESRs) are crucial to the maintenance of this barrier and function to detect and respond to perturbations in the envelope, caused by environmental stresses. Pathogenic bacteria are exposed to an array of challenging and stressful conditions during their lifecycle and, in particular, during infection of a host. As such, maintenance of envelope homeostasis is essential to their ability to successfully cause infection. This review will discuss our current understanding of the σ^E- and Cpx-regulated ESRs, with a specific focus on their role in the virulence of a number of model pathogens.

• Cpx response
• Gram-negative bacteria
• envelope stress
• pathogenesis
• sigmaE response

• bacterial infection
• infection

• Animals
• Evolution, Molecular
• Humans
• Plague/diagnosis
• Plague/epidemiology
• Plague/microbiology
• Plague/therapy
• Virulence Factors/genetics
• Yersinia pestis/genetics
• Yersinia pestis/immunology
• Yersinia pestis/pathogenicity

• Institut Pasteur
• Université Paris Diderot (Paris Diderot)

Yersinia pestis, the causative agent of plague, possesses a number of virulence mechanisms that allows it to survive and proliferate during its interaction with the host. To discover additional infection-specific Y. pestis factors, a transposon site hybridization (TraSH)-based genome-wide screen was employed to identify genomic regions required for its survival during cellular infection. In addition to several well-characterized infection-specific genes, this screen identified three chromosomal genes (y3397, y3399, and y3400), located in an apparent operon, that promoted successful infection. Each of these genes is predicted to encode a leucine-rich repeat family protein with or without an associated ubiquitin E3 ligase domain. These genes were designated Yersinia leucine-rich repeat gene A (ylrA), B (ylrB), and C (ylrC). Engineered strains with deletions of y3397 (ylrC), y3399 (ylrB), or y3400 (ylrA), exhibited infection defects both in cultured cells and in the mouse. C-terminal FLAG-tagged YlrA, YlrB, and YlrC were secreted by Y. pestis in the absence but not the presence of extracellular calcium and deletions of the DNA sequences encoding the predicted N-terminal type III secretion signals of YlrA, YlrB, and YlrC prevented their secretion, indicating that these proteins are substrates of the type III secretion system (T3SS). Further strengthening the connection with the T3SS, YlrB was readily translocated into HeLa cells and expression of the YlrA and YlrC proteins in yeast inhibited yeast growth, indicating that these proteins may function as anti-host T3S effector proteins.

• Yersinia
• leucine rich repeats
• mice
• pathogenesis
• plague
• type III secretion

A pathogenic lifestyle is inextricably linked with the constant necessity of facing various challenges exerted by the external environment (both within and outside the host). To successfully colonize the host and establish infection, pathogens have evolved sophisticated systems to combat the host defense mechanisms and also to be able to withstand adverse environmental conditions. Proteases, as crucial components of these systems, are involved in a variety of processes associated with infection. In phytopathogenic bacteria, they play important regulatory roles and modulate the expression and functioning of various virulence factors. Secretory proteases directly help avoid recognition by the plant immune systems, and contribute to the deactivation of the defense response pathways. Finally, proteases are important components of protein quality control systems, and thus enable maintaining homeostasis in stressed bacterial cells. In this review, we discuss the known protease functions and protease-regulated signaling processes associated with virulence of plant pathogenic bacteria.

• T3SS
• bacterial virulence
• effector proteases
• extracellular proteases
• plant pathogenic bacteria
• regulatory proteolysis

• Bacteria/metabolism
• Bacterial Infections/metabolism
• Peptide Hydrolases/metabolism
• Plant Diseases
• Plant Proteins/metabolism
• Plants/metabolism
• Virulence Factors/metabolism

• Correlates of protection
• F1
• IgG
• Live vaccine
• Plague
• Yersinia pestis
• Yersinia pseudotuberculosis

• Chlamydia psittaci
• T3SS
• cellular localization
• cysteine desulfurase
• mitochondria-mediated pathway

• Bacterial infections
• Immunology
• Macrophages
• Microbiology

• LuxR
• N-acylhomoserine lactones
• Yersinia enterocolitica
• cell attachment
• motility
• quorum sensing
• virulence plasmid maintenance

• In vivo bioluminescence imaging
• Plague
• Yersinia pestis
• Yersinia pseudotuberculosis

The World Health Organization has categorized plague as a re-emerging disease and the potential for Yersinia pestis to also be used as a bioweapon makes the identification of new drug targets against this pathogen a priority. Environmental temperature is a key signal which regulates virulence of the bacterium. The bacterium normally grows outside the human host at 28 °C. Therefore, understanding the mechanisms that the bacterium used to adapt to a mammalian host at 37 °C is central to the development of vaccines or drugs for the prevention or treatment of human disease.

Using a library of over 1 million Y. pestis CO92 random mutants and transposon-directed insertion site sequencing, we identified 530 essential genes when the bacteria were cultured at 28 °C. When the library of mutants was subsequently cultured at 37 °C we identified 19 genes that were essential at 37 °C but not at 28 °C, including genes which encode proteins that play a role in enabling functioning of the type III secretion and in DNA replication and maintenance. Using genome-scale metabolic network reconstruction we showed that growth conditions profoundly influence the physiology of the bacterium, and by combining computational and experimental approaches we were able to identify 54 genes that are essential under a broad range of conditions.

Using an integrated computational-experimental approach we identify genes which are required for growth at 37 °C and under a broad range of environments may be the best targets for the development of new interventions to prevent or treat plague in humans.

The online version of this article (doi:10.1186/s12866-017-1073-8) contains supplementary material, which is available to authorized users.

• Essential genes
• Metabolic model
• Plague
• TRADIS
• Transposon
• Yersinia pestis

• Yersinia pestis
• free-living amoeba
• interepizootic plague

Yersinia enterocolitica is a widespread Gram-negative bacterium that causes gastrointestinal disease and other clinical manifestations in humans. Potentially pathogenic Y. enterocolitica has been isolated in Brazil, from human, environmental, food, and animal sources. Herein we report a genome sequence of Y. enterocolitica subsp. palearctica strain YE 19, serotype O:3, biotype 4, sequence type 18, with virulence determinants isolated from human blood in Rio de Janeiro in 2005. The results corroborate other findings that this strain harbors a set of virulence determinants that could play a role in host pathoadaptation and may also justify the successful dissemination of bioserotype 4/O:3 in Brazil. The presence of strains harboring all of these virulence genes in Brazil is a potential threat to young children and immunocompromised individuals, for whom yersiniosis are a significant source of morbidity and mortality. The results of a genomic data analysis will help understand the virulence of Brazilian strains and provide data for Y. enterocolitica studies worldwide.

• Brazil
• Next-generation sequencing
• Virulence
• Yersinia enterocolitica

• Genome, Bacterial/genetics
• High-Throughput Nucleotide Sequencing
• Humans
• Virulence Factors/genetics
• Yersinia enterocolitica/genetics
• Yersinia enterocolitica/pathogenicity

Among the many medical applications of systems biology, we contend that infectious disease is one of the most important and tractable targets. We take the view that the complexity of the immune system is an inevitable consequence of its evolution, and this complexity has frustrated reductionist efforts to develop host-directed therapies for infection. However, since hosts vary widely in susceptibility and tolerance to infection, host-directed therapies are likely to be effective, by altering the biology of a susceptible host to induce a response more similar to a host who survives. Such therapies should exert minimal selection pressure on organisms, thus greatly decreasing the probability of pathogen resistance developing.

A systems medicine approach to infection has the potential to provide new solutions to old problems: to identify host traits that are potentially amenable to therapeutic intervention, and the host immune factors that could be targeted by host-directed therapies. Furthermore, undiscovered sub-groups with different responses to treatment are almost certain to exist among patients presenting with life-threatening infection, since this population is markedly clinically heterogeneous. A major driving force behind high-throughput clinical phenotyping studies is the aspiration that these subgroups, hitherto opaque to observation, may be observed in the data generated by new technologies. Subgroups of patients are unlikely to be static – serial clinical and biological phenotyping may reveal different trajectories through the pathophysiology of disease, in which different therapeutic approaches are required.

We suggest there are two major goals for systems biology in infection medicine: (1) to identify subgroups of patients that share treatable features; and, (2) to integrate high-throughput data from clinical and in vitro sources in order to predict tractable therapeutic targets with the potential to alter disease trajectories for individual patients.

•

High throughput technologies can reveal clinical patterns in infection that were previously opaque.

• Endotypes
• Genomics
• Infectious disease
• Transcriptomics
• Treatable traits

• SufI
• Tat pathway
• Yersinia pseudotuberculosis
• mesenteric lymph nodes
• neutrophils
• virulence

• Yersinia outer proteins
• Yop
• auto-inflammatory disease
• cell-penetrating effector protein
• immunomodulatory
• type 3 secretion system

On record, there are 17 species in the Yersinia genus, of which three are known to be pathogenic to human. While the chromosomal and pYV (or pCD1) plasmid-borne virulence genes as well as pathogenesis of these three species are well studied, their genomic evolution is poorly understood. Our study aims to predict the key evolutionary events that led to the emergence of pathogenic Yersinia species by analyzing gene gain-and-loss, virulence genes, and “Clustered regularly-interspaced short palindromic repeats”. Our results suggest that the most recent ancestor shared by the human pathogenic Yersinia was most probably an environmental species that had adapted to the human body. This might have led to ecological specialization that diverged Yersinia into ecotypes and distinct lineages based on differential gene gain-and-loss in different niches. Our data also suggest that Y. pseudotuberculosis group might be the donor of the ail virulence gene to Y. enterocolitica. Hence, we postulate that evolution of human pathogenic Yersinia might not be totally in parallel, but instead, there were lateral gene transfer events. Furthermore, the presence of virulence genes seems to be important for the positive selection of virulence plasmid. Our studies provide better insights into the evolutionary biology of these bacteria.

Bacterial pathogens display an impressive arsenal of molecular mechanisms that allow survival in diverse host niches. Subversion of plasma membrane and cytoskeletal functions are common themes associated to infection by both extracellular and intracellular pathogens. Moreover, intracellular pathogens modify the structure/stability of their membrane-bound compartments and escape degradation from phagocytic or autophagic pathways. Here, we review the manipulation of host membranes by Listeria monocytogenes, Francisella tularensis, Shigella flexneri and Yersinia spp. These four bacterial model pathogens exemplify generalized strategies as well as specific features observed during bacterial infection processes.

• Francisella tularensis
• Listeria monocytogenes
• Membrane trafficking
• Phagocytosis
• Shigella flexneri
• Yersinia pseudotuberculosis

The iron overload disorder hereditary hemochromatosis (HH) predisposes humans to serious disseminated infection with pathogenic Yersinia as well as several other pathogens. Recently, we showed that the iron-sulfur cluster coordinating transcription factor IscR is required for type III secretion in Y. pseudotuberculosis by direct control of the T3SS master regulator LcrF. In E. coli and Yersinia, IscR levels are predicted to be regulated by iron bioavailability, oxygen tension, and oxidative stress, such that iron depletion should lead to increased IscR levels. To investigate how host iron overload influences Y. pseudotuberculosis virulence and the requirement for the Ysc type III secretion system (T3SS), we utilized two distinct murine models of HH: hemojuvelin knockout mice that mimic severe, early-onset HH as well as mice with the Hfe^{C282Y∕C282Y} mutation carried by 10% of people of Northern European descent, associated with adult-onset HH. Hjv^−∕− and Hfe^{C282Y∕C282Y} transgenic mice displayed enhanced colonization of deep tissues by Y. pseudotuberculosis following oral inoculation, recapitulating enhanced susceptibility of humans with HH to disseminated infection with enteropathogenic Yersinia. Importantly, HH mice orally infected with Y. pseudotuberculosis lacking the T3SS-encoding virulence plasmid, pYV, displayed increased deep tissue colonization relative to wildtype mice. Consistent with previous reports using monocytes from HH vs. healthy donors, macrophages isolated from Hfe^{C282Y∕C282Y} mice were defective in Yersinia uptake compared to wildtype macrophages, indicating that the anti-phagocytic property of the Yersinia T3SS plays a less important role in HH animals. These data suggest that Yersinia may rely on distinct virulence factors to cause disease in healthy vs. HH hosts.

• HFE
• IscR
• Yersinia pseudotuberculosis
• hemochromatosis
• hemojuvelin
• type III secretion system

The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six ‘effector’ proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen.

• Yersinia pestis
• ail locus
• pH6 antigen
• virulence factors
• yersiniae

• Escherichia coli
• Yersinia enterocolitica
• cell envelope
• stress response
• virulence