scholarly journals Evolution and Virulence Contributions of the Autotransporter Proteins YapJ and YapK of Yersinia pestis CO92 and Their Homologs in Y. pseudotuberculosis IP32953

2012 ◽  
Vol 80 (10) ◽  
pp. 3693-3705 ◽  
Author(s):  
Jonathan D. Lenz ◽  
Brenda R. S. Temple ◽  
Virginia L. Miller
Keyword(s):  
Yersinia Pestis ◽  
Yersinia Pseudotuberculosis ◽  
Systemic Infection ◽  
Content Type ◽  
Sequence Identity ◽  
Homologous Genes ◽  
C Terminus ◽  
Gastrointestinal Pathogen ◽  
Numerous Type ◽  
High Level

ABSTRACTYersinia pestis, the causative agent of plague, evolved from the gastrointestinal pathogenYersinia pseudotuberculosis. Both species have numerous type Va autotransporters, most of which appear to be highly conserved. InY. pestisCO92, the autotransporter genesyapKandyapJshare a high level of sequence identity. By comparingyapKandyapJto three homologous genes inY. pseudotuberculosisIP32953 (YPTB0365, YPTB3285, and YPTB3286), we show thatyapKis conserved inY. pseudotuberculosis, whileyapJis unique toY. pestis. All of these autotransporters exhibit >96% identity in the C terminus of the protein and identities ranging from 58 to 72% in their N termini. By extending this analysis to include homologous sequences from numerousY. pestisandY. pseudotuberculosisstrains, we determined that these autotransporters cluster into a YapK (YPTB3285) class and a YapJ (YPTB3286) class. The YPTB3286-like gene of mostY. pestisstrains appears to be inactivated, perhaps in favor of maintainingyapJ. Since autotransporters are important for virulence in many bacterial pathogens, includingY. pestis, any change in autotransporter content should be considered for its impact on virulence. Using established mouse models ofY. pestisinfection, we demonstrated that despite the high level of sequence identity,yapKis distinct fromyapJin its contribution to disseminatedY. pestisinfection. In addition, a mutant lacking both of these genes exhibits an additive attenuation, suggesting nonredundant roles foryapJandyapKin systemicY. pestisinfection. However, the deletion of the homologous genes inY. pseudotuberculosisdoes not seem to impact the virulence of this organism in orogastric or systemic infection models.

scholarly journals Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen

2016 ◽  
Vol 84 (4) ◽  
pp. 1083-1091 ◽  
Author(s):  
Ryan McCormack ◽  
Wael Bahnan ◽  
Niraj Shrestha ◽  
Justin Boucher ◽  
Marcella Barreto ◽  
...  
Keyword(s):  
Bacterial Pathogen ◽  
Virulence Gene ◽  
Systemic Infection ◽  
Protective Role ◽  
Host Cells ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Membrane Bound ◽  
High Level ◽  
Macpf Domain

The host-encoded Perforin-2 (encoded by the macrophage-expressed gene 1,Mpeg1), which possesses a pore-forming MACPF domain, reduces the viability of bacterial pathogens that reside within membrane-bound compartments. Here, it is shown that Perforin-2 also restricts the proliferation of the intracytosolic pathogenListeria monocytogenes. Within a few hours of systemic infection, the massive proliferation ofL. monocytogenesinPerforin-2−/−mice leads to a rapid appearance of acute disease symptoms. We go on to show in culturedPerforin-2−/−cells that the vacuole-to-cytosol transitioning ofL. monocytogenesis greatly accelerated. Unexpectedly, we found that inPerforin-2−/−macrophages,Listeria-containing vacuoles quickly (≤15 min) acidify, and that this was coincident with greater virulence gene expression, likely accounting for the more rapid translocation ofL. monocytogenesto its replicative niche in the cytosol. This hypothesis was supported by our finding that aL. monocytogenesstrain expressing virulence factors at a constitutively high level replicated equally well inPerforin-2+/+andPerforin-2−/−macrophages. Our findings suggest that the protective role of Perforin-2 against listeriosis is based on it limiting the intracellular replication of the pathogen. This cellular activity of Perforin-2 may derive from it regulating the acidification ofListeria-containing vacuoles, thereby depriving the pathogen of favorable intracellular conditions that promote its virulence gene activity.

scholarly journals Comprehensive Analysis Reveals the Evolution and Pathogenicity of Aeromonas, Viewed from Both Single Isolated Species and Microbial Communities

mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Chaofang Zhong ◽  
Maozhen Han ◽  
Pengshuo Yang ◽  
Chaoyun Chen ◽  
Hui Yu ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Microbial Communities ◽  
Virulence Factors ◽  
Evolutionary Dynamics ◽  
Content Type ◽  
Pan Genome ◽  
Gastrointestinal Pathogen ◽  
High Level ◽  
Core Genes ◽  
Isolated Species

ABSTRACT The genus Aeromonas is a common gastrointestinal pathogen associated with human and animal infections. Due to the high level of cross-species similarity, their evolutionary dynamics and genetic diversity are still fragmented. Hereby, we investigated the pan-genomes of 29 Aeromonas species, as well as Aeromonas species in microbial communities, to clarify their evolutionary dynamics and genetic diversity, with special focus on virulence factors and horizontal gene transfer events. Our study revealed an open pan-genome of Aeromonas containing 10,144 gene families. These Aeromonas species exhibited different functional constraints, with the single-copy core genes and most accessory genes experiencing purifying selection. The significant congruence between core genome and pan-genome trees revealed that core genes mainly affected evolutionary divergences of Aeromonas species. Gene gains and losses revealed a high level of genome plasticity, exhibited by hundreds of gene expansions and contractions, horizontally transferred genes, and mobile genetic elements. The selective constraints shaped virulence gene pools of these Aeromonas strains, where genes encoding hemolysin were ubiquitous. Of these strains, Aeromonas aquatica MX16A seemed to be more resistant, as it harbored most resistance genes. Finally, the virulence factors of Aeromonas in microbial communities were quite dynamic in response to environment changes. For example, the virulence diversity of Aeromonas in microbial communities could reach levels that match some of the most virulent Aeromonas species (such as A. hydrophila) in penetrated-air and modified-air packaging. Our work shed some light onto genetic diversity, evolutionary history, and functional features of Aeromonas, which could facilitate the detection and prevention of infections. IMPORTANCE Aeromonas has long been known as a gastrointestinal pathogen, yet it has many species whose evolutionary dynamics and genetic diversity had been unclear until now. We have conducted pan-genome analysis for 29 Aeromonas species and revealed a high level of genome plasticity exhibited by hundreds of gene expansions and contractions, horizontally transferred genes, and mobile genetic elements. These species also contained many virulence factors both identified from single isolated species and microbial community. This pan-genome study could elevate the level for detection and prevention of Aeromonas infections.

scholarly journals Complete Genome Assembly of Yersinia pseudotuberculosis IP2666pIB1

2019 ◽  
Vol 8 (7) ◽  
Author(s):  
Adam Zoubeidi ◽  
Leah Schwiesow ◽  
Victoria Auerbuch ◽  
Hanh N. Lam
Keyword(s):  
Yersinia Pestis ◽  
Genome Assembly ◽  
Complete Genome ◽  
Yersinia Pseudotuberculosis ◽  
Model Organism ◽  
Genomic Analysis ◽  
Bacterial Pathogenesis ◽  
Bacterial Virulence ◽  
Human Pathogen ◽  
Content Type

Yersinia pseudotuberculosis, closely related to Yersinia pestis, is a human pathogen and model organism for studying bacterial pathogenesis. To aid in genomic analysis and understanding bacterial virulence, we sequenced and assembled the complete genome of the human pathogen Yersinia pseudotuberculosis IP2666pIB1.

scholarly journals High Prevalence and Predominance of the aph(2″)-If Gene Conferring Aminoglycoside Resistance in Campylobacter

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Hong Yao ◽  
Dejun Liu ◽  
Yang Wang ◽  
Qijing Zhang ◽  
Zhangqi Shen
Keyword(s):  
Horizontal Transmission ◽  
Foodborne Pathogen ◽  
Systemic Infection ◽  
Campylobacter Coli ◽  
Aminoglycoside Resistance ◽  
Content Type ◽  
High Prevalence ◽  
Gentamicin Resistance ◽  
Long Range Pcr ◽  
High Level

ABSTRACT Campylobacter is a major foodborne pathogen, and previous studies revealed that Campylobacter isolates from food-producing animals are increasingly resistant to gentamicin in China. The molecular epidemiology and genetic mechanisms responsible for gentamicin resistance in China have not been well understood. In this study, 607 Campylobacter isolates of chicken and swine origins collected in 2014 were analyzed, revealing that 15.6% (25/160) of the Campylobacter jejuni isolates and 79.9% (357/447) of the Campylobacter coli isolates were resistant to gentamicin. PCR detection of the gentamicin resistance genes indicated that aph(2″)-If was more prevalent than the previously identified aacA/aphD gene and has become the dominant gentamicin resistance determinant in Campylobacter. Transformation and whole-genome sequencing as well as long-range PCR discovered that aph(2″)-If was located on a chromosomal segment inserted between two conserved genes, Cj0299 and panB. Cloning of aph(2″)-If into gentamicin-susceptible C. jejuni NCTC 11168 confirmed its function in conferring high-level resistance to gentamicin and kanamycin. Molecular typing by pulsed-field gel electrophoresis suggested that both regional expansion of a particular clone and horizontal transmission were involved in the dissemination of the aph(2″)-If gene in Campylobacter. To our knowledge, this is the first report describing the high prevalence of a chromosomally encoded aph(2″)-If gene in Campylobacter. The high prevalence and predominance of this gene might be driven by the use of aminoglycoside antibiotics in food animal production in China and potentially compromise the usefulness of gentamicin as a therapeutic agent for Campylobacter-associated systemic infection.

scholarly journals The Tat Substrate SufI Is Critical for the Ability of Yersinia pseudotuberculosis To Cause Systemic Infection

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Ummehan Avican ◽  
Tugrul Doruk ◽  
Yngve Östberg ◽  
Anna Fahlgren ◽  
Åke Forsberg
Keyword(s):  
Stress Responses ◽  
Pathogenic Bacteria ◽  
Yersinia Pseudotuberculosis ◽  
Systemic Infection ◽  
Mesenteric Lymph Nodes ◽  
Content Type ◽  
Twin Arginine Translocation ◽  
Genes Encoding ◽  
Folded Proteins

ABSTRACT The twin arginine translocation (Tat) system targets folded proteins across the inner membrane and is crucial for virulence in many important human-pathogenic bacteria. Tat has been shown to be required for the virulence of Yersinia pseudotuberculosis, and we recently showed that the system is critical for different virulence-related stress responses as well as for iron uptake. In this study, we wanted to address the role of the Tat substrates in in vivo virulence. Therefore, 22 genes encoding potential Tat substrates were mutated, and each mutant was evaluated in a competitive oral infection of mice. Interestingly, a ΔsufI mutant was essentially as attenuated for virulence as the Tat-deficient strain. We also verified that SufI was Tat dependent for membrane/periplasmic localization in Y. pseudotuberculosis. In vivo bioluminescent imaging of orally infected mice revealed that both the ΔsufI and ΔtatC mutants were able to colonize the cecum and Peyer's patches (PPs) and could spread to the mesenteric lymph nodes (MLNs). Importantly, at this point, neither the ΔtatC mutant nor the ΔsufI mutant was able to spread systemically, and they were gradually cleared. Immunostaining of MLNs revealed that both the ΔtatC and ΔsufI mutants were unable to spread from the initial infection foci and appeared to be contained by neutrophils, while wild-type bacteria readily spread to establish multiple foci from day 3 postinfection. Our results show that SufI alone is required for the establishment of systemic infection and is the major cause of the attenuation of the ΔtatC mutant.

scholarly journals Proteolytic processing of the Yersinia pestis YapG autotransporter by the omptin protease Pla and the contribution of YapG to murine plague pathogenesis

2013 ◽  
Vol 62 (8) ◽  
pp. 1124-1134 ◽  
Author(s):  
M. Chelsea Lane ◽  
Jonathan D. Lenz ◽  
Virginia L. Miller
Keyword(s):  
Yersinia Pestis ◽  
Mouse Models ◽  
Yersinia Pseudotuberculosis ◽  
Proteolytic Processing ◽  
Complex Life Cycle ◽  
Bacterial Surface ◽  
Bacterial Membranes ◽  
Gastrointestinal Pathogen ◽  
Wide Range ◽  
Associated Functions

Autotransporter protein secretion represents one of the simplest forms of secretion across Gram-negative bacterial membranes. Once secreted, autotransporter proteins either remain tethered to the bacterial surface or are released following proteolytic cleavage. Autotransporters possess a diverse array of virulence-associated functions such as motility, cytotoxicity, adherence and autoaggregation. To better understand the role of autotransporters in disease, our research focused on the autotransporters of Yersinia pestis, the aetiological agent of plague. Y. pestis strain CO92 has nine functional conventional autotransporters, referred to as Yaps for Yersinia autotransporter proteins. Three Yaps have been directly implicated in virulence using established mouse models of plague infection (YapE, YapJ and YapK). Whilst previous studies from our laboratory have shown that most of the CO92 Yaps are cell associated, YapE and YapG are processed and released by the omptin protease Pla. In this study, we identified the Pla cleavage sites in YapG that result in many released forms of YapG in Y. pestis, but not in the evolutionarily related gastrointestinal pathogen, Yersinia pseudotuberculosis, which lacks Pla. Furthermore, we showed that YapG does not contribute to Y. pestis virulence in established mouse models of bubonic and pneumonic infection. As Y. pestis has a complex life cycle involving a wide range of mammalian hosts and a flea vector for transmission, it remains to be elucidated whether YapG has a measurable role in any other stage of plague disease.

scholarly journals A Type III Secretion System Inhibitor Targets YopD while Revealing Differential Regulation of Secretion in Calcium-Blind Mutants of Yersinia pestis

2013 ◽  
Vol 58 (2) ◽  
pp. 839-850 ◽  
Author(s):  
Danielle L. Jessen ◽  
David S. Bradley ◽  
Matthew L. Nilles
Keyword(s):  
Yersinia Pestis ◽  
Type Iii Secretion ◽  
Yersinia Pseudotuberculosis ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Secretion Systems ◽  
Content Type ◽  
Type Iii ◽  
Regulatory Processes ◽  
Secretion Inhibition

ABSTRACTNumerous Gram-negative pathogens rely upon type III secretion (T3S) systems to cause disease. Several small-molecule inhibitors of the type III secretion systems have been identified; however, few targets of these inhibitors have been elucidated. Here we report that 2,2′-thiobis-(4-methylphenol) (compound D), inhibits type III secretion inYersinia pestis,Yersinia pseudotuberculosis, andPseudomonas aeruginosa. YopD, a protein involved in the formation of the translocon and regulatory processes of the type III secretion system, appears to play a role in the inhibition of secretion by compound D. The use of compound D in T3S regulatory mutants demonstrated a difference in secretion inhibition in the presence and absence of calcium. Interestingly, compound D was effective only under conditions without calcium, indicating that a secretion-active needle structure may be necessary for compound D to inhibit secretion.

scholarly journals Invasion of Epithelial Cells by Yersinia pestis: Evidence for a Y. pestis-Specific Invasin

2000 ◽  
Vol 68 (8) ◽  
pp. 4523-4530 ◽  
Author(s):  
Clarissa Cowan ◽  
Heather A. Jones ◽  
Yasemin H. Kaya ◽  
Robert D. Perry ◽  
Susan C. Straley
Keyword(s):  
Epithelial Cells ◽  
Yersinia Pestis ◽  
Hela Cells ◽  
Yersinia Pseudotuberculosis ◽  
Iron Status ◽  
Systemic Infection ◽  
Thermally Induced ◽  
Gentamicin Protection Assay ◽  
Negative Findings ◽  
Fetal Bovine

ABSTRACT The causative agent of plague, Yersinia pestis, is regarded as being noninvasive for epithelial cells and lacks the major adhesins and invasins of its enteropathogenic relatives Yersinia enterocolitica and Yersinia pseudotuberculosis. However, there are studies indicating that Y. pestisinvades and causes systemic infection from ingestive and aerogenic routes of infection. Accordingly, we developed a gentamicin protection assay and reexamined invasiveness of Y. pestis for HeLa cells. By optimizing this assay, we discovered that Y. pestis is highly invasive. Several factors, including the presence of fetal bovine serum, the configuration of the tissue culture plate, the temperature at which the bacteria are grown, and the presence of the plasminogen activator protease Pla-encoding plasmid pPCP1, were found to influence invasiveness strongly. Suboptimal combinations of these factors may have contributed to negative findings by previous studies attempting to demonstrate invasion by Y. pestis. Invasion of HeLa cells was strongly inhibited by cytochalasin D and modestly inhibited by colchicine, indicating strong and modest respective requirements for microfilaments and microtubules. We found no significant effect of the iron status of yersiniae or of the pigmentation locus on invasion and likewise no significant effect of the Yops regulon. However, an unidentified thermally induced property (possibly the Y. pestis-specific capsular protein Caf1) did inhibit invasiveness significantly, and the plasmid pPCP1, unique to Y. pestis, was essential for highly efficient invasion. pPCP1 encodes an invasion-promoting factor and not just an adhesin, because Y. pestis lacking this plasmid still adhered to HeLa cells. These studies have enlarged our picture ofY. pestis biology and revealed the importance of properties that are unique to Y. pestis.

scholarly journals Flagellin-Mediated Protection against Intestinal Yersinia pseudotuberculosis Infection Does Not Require Interleukin-22

2016 ◽  
Vol 85 (2) ◽  
Author(s):  
Rémi Porte ◽  
Laurye Van Maele ◽  
Natalia Muñoz-Wolf ◽  
Benoit Foligné ◽  
Laure Dumoutier ◽  
...  
Keyword(s):  
Yersinia Pseudotuberculosis ◽  
Viral Infections ◽  
Specific Effect ◽  
Systemic Infection ◽  
Bacterial Count ◽  
Lymphoid Cells ◽  
Protective Effects ◽  
Content Type ◽  
Interleukin 22 ◽  
Tlr4 Agonist

ABSTRACT Signaling through Toll-like receptors (TLRs), the main receptors in innate immunity, is essential for the defense of mucosal surfaces. It was previously shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate, transient interleukin-22 (IL-22)-dependent antimicrobial response to bacterial or viral infections of the mucosa. This process was dependent on the activation of type 3 innate lymphoid cells (ILCs). The objective of the present study was to analyze the effects of flagellin treatment in a murine model of oral infection with Yersinia pseudotuberculosis (an invasive, Gram-negative, enteropathogenic bacterium that targets the small intestine). We found that systemic administration of flagellin significantly increased the survival rate after intestinal infection (but not systemic infection) by Y. pseudotuberculosis. This protection was associated with a low bacterial count in the gut and the spleen. In contrast, no protection was afforded by administration of the TLR4 agonist lipopolysaccharide, suggesting the presence of a flagellin-specific effect. Lastly, we found that TLR5- and MyD88-mediated signaling was required for the protective effects of flagellin, whereas neither lymphoid cells nor IL-22 was involved.

scholarly journals Resistance to Yersinia pestis Infection Decreases with Age in B10.T(6R) Mice

2011 ◽  
Vol 79 (11) ◽  
pp. 4438-4446 ◽  
Author(s):  
Nathaniel D. Lambert ◽  
Deanna M. Langfitt ◽  
Matthew L. Nilles ◽  
David S. Bradley
Keyword(s):  
Yersinia Pestis ◽  
Immune Cells ◽  
Immunohistochemical Staining ◽  
Immune Cell ◽  
Lethal Dose ◽  
Systemic Infection ◽  
Immune Cell Infiltration ◽  
Middle Aged ◽  
Content Type ◽  
Aged Mice

ABSTRACTWe demonstrate that 2-month-old female B10.T(6R) mice are highly resistant to systemic infection with the KIM5 strain ofYersinia pestisand that B10.T(6R) mice become susceptible toY. pestisinfection by the age of 5 months. In this study, young (2-month-old) and middle-aged (5- to 12-month-old) B10.T(6R) mice were infected with equal CFU counts ofY. pestis. The 50% lethal dose (LD50) for young B10.T(6R) mice was ∼1.4 × 104CFU, while middle-aged B10.T(6R) mice exhibited an LD50of ∼60 CFU. Elevated bacterial burdens were found in the spleens of middle-aged mice at 24 and 60 h and in the livers at 60 h postinfection. Immune cell infiltration was greater in the livers of resistant young mice than in those of middle-aged mice and mice of the susceptible C57BL/6N strain. Unlike susceptible mice, young B10.T(6R) mice did not develop necrotic lesions throughout the liver. Instead, livers from young B10.T(6R) mice contained granuloma-like structures. Immunohistochemical staining of liver sections from these mice at 60 h postinfection revealed that the majority of immune cells present in these structures were neutrophils. These findings suggest that resistance to plague in B10.T(6R) mice correlates with early formation of neutrophilic lesions in the liver.

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