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Chemico-biological Interactions Apr 2017Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant...
Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant strains of Yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. Although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. The vaccine strategy described here is based on an oral vaccination with an attenuated strain of Yersinia pseudotuberculosis. Indeed, this species is genetically almost identical to Y. pestis, but has a much lower pathogenicity and a higher genomic stability. Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953 were performed to generate a safe and immunogenic vaccine. Genes coding for three essential virulence factors were deleted from this strain. To increase cross-species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then generated. For this, the Y. pestis caf operon, which encodes F1, was inserted first on a plasmid, and subsequently into the chromosome. The successive steps achieved to reach maximal vaccine potential are described, and how each step affected bacterial virulence and the development of a protective immune response is discussed. The final version of the vaccine, named VTnF1, provides a highly efficient and long-lasting protection against both bubonic and pneumonic plague after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist or could be engineered, we also analyzed the protection conferred by the vaccine against such strain and found that it also confers full protection against the two forms of plague. Thus, the properties of VTnF1 makes it one of the most efficient candidate vaccine for mass vaccination in tropical endemic areas as well as for populations exposed to bioterrorism.
Topics: Administration, Oral; Animals; Bacterial Proteins; Plague; Plague Vaccine; Swine; Vaccination; Vaccines, Synthetic; Virulence; Yersinia pestis; Yersinia pseudotuberculosis
PubMed: 27046452
DOI: 10.1016/j.cbi.2016.03.030 -
Journal of Clinical Microbiology May 2021is an important pathogen for both humans and animals. It can infect livestock, as well as pets and wild animals. During recent years, a number of reports have described...
is an important pathogen for both humans and animals. It can infect livestock, as well as pets and wild animals. During recent years, a number of reports have described the isolation of from zoo animals, mainly birds and mammals, for which the infection was mostly lethal. Between 2005 and 2019, there were at least 17 cases of deceased mammals, belonging to five different species, which suffered from a infection at the Zoo Wuppertal, Germany. Since only scarce information exists on the properties of from zoo animals, we characterized eight isolates, covering all infected species, in detail. All isolates were members of biotype 1, but belonged to five serotypes, five sequence types (STs), and seven core-genome multilocus sequence types (cgMLSTs). Using pulsed-field gel electrophoresis (PFGE) analysis and whole-genome sequencing (WGS), the seven isolates could be discriminated from each other. They differed significantly regarding their virulence genes and mobile genetic elements. While the virulence plasmid pYV existed in all serotypes (five isolates), a complete high-pathogenicity island (HPI) was detected only in the serotypes O:1a, O:1b, and O:13 (four isolates), but not in O:2a and O:2b. Similarly, the content of other plasmids and prophages varied greatly between the isolates. The data demonstrate that the deceased mammals were infected by seven individual isolates and not by a single type predominating in the zoo animals.
Topics: Animals; Animals, Zoo; Germany; Humans; Mammals; Yersinia enterocolitica; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis Infections
PubMed: 33789956
DOI: 10.1128/JCM.03125-20 -
Cellular and Molecular Life Sciences :... Aug 2017Adaptive immunity critically contributes to control acute infection with enteropathogenic Yersinia pseudotuberculosis; however, the role of CD4 T cell subsets in...
Adaptive immunity critically contributes to control acute infection with enteropathogenic Yersinia pseudotuberculosis; however, the role of CD4 T cell subsets in establishing infection and allowing pathogen persistence remains elusive. Here, we assessed the modulatory capacity of Y. pseudotuberculosis on CD4 T cell differentiation. Using in vivo assays, we report that infection with Y. pseudotuberculosis resulted in enhanced priming of IL-17-producing T cells (Th17 cells), whereas induction of Foxp3 regulatory T cells (Tregs) was severely disrupted in gut-draining mesenteric lymph nodes (mLNs), in line with altered frequencies of tolerogenic and proinflammatory dendritic cell (DC) subsets within mLNs. Additionally, by using a DC-free in vitro system, we could demonstrate that Y. pseudotuberculosis can directly modulate T cell receptor (TCR) downstream signaling within naïve CD4 T cells and Tregs via injection of effector molecules through the type III secretion system, thereby affecting their functional properties. Importantly, modulation of naïve CD4 T cells by Y. pseudotuberculosis resulted in an enhanced Th17 differentiation and decreased induction of Foxp3 Tregs in vitro. These findings shed light to the adjustment of the Th17-Treg axis in response to acute Y. pseudotuberculosis infection and highlight the direct modulation of CD4 T cell subsets by altering their TCR downstream signaling.
Topics: Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; Female; Forkhead Transcription Factors; Host-Pathogen Interactions; Intestines; Mice, Inbred BALB C; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes, Regulatory; Th17 Cells; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis Infections
PubMed: 28378044
DOI: 10.1007/s00018-017-2516-y -
Virulence Dec 2021Adhesins facilitate bacterial colonization and invasion of host tissues and are considered virulence factors, but their impact on immune-mediated damage as a driver of...
Adhesins facilitate bacterial colonization and invasion of host tissues and are considered virulence factors, but their impact on immune-mediated damage as a driver of pathogenesis remains unclear. encodes for a ultivalent dhesion olecule (MAM), a mammalian cell entry (MCE) family protein and adhesin. MAMs are widespread in Gram-negative bacteria and enable enteric bacteria to colonize epithelial tissues. Their role in bacterial interactions with the host innate immune system and contribution to pathogenicity remains unclear. Here, we investigated how MAM contributes to pathogenesis during infection of the insect model. We show that MAM is required for efficient bacterial binding and uptake by hemocytes, the host phagocytes. interactions with insect and mammalian phagocytes are determined by bacterial and host factors. Loss of MAM, and deficient microbe-phagocyte interaction, increased pathogenesis in . Diminished phagocyte association also led to increased bacterial clearance. Furthermore, that failed to engage phagocytes hyperactivated humoral immune responses, most notably melanin production. Despite clearing the pathogen, excessive melanization also increased phagocyte death and host mortality. Our findings provide a basis for further studies investigating how microbe- and host-factors integrate to drive pathogenesis in a tractable experimental system.
Topics: Adhesins, Bacterial; Animals; Hemocytes; Host-Pathogen Interactions; Larva; Moths; Phagocytes; Virulence Factors; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis Infections
PubMed: 33550901
DOI: 10.1080/21505594.2021.1878672 -
Veterinary Microbiology Jun 2022A Yersinia pseudotuberculosis outbreak was diagnosed in a male turkey flock in Finland. Y. pseudotuberculosis is a quite rare zoonotic bacterium, which typically causes...
A Yersinia pseudotuberculosis outbreak was diagnosed in a male turkey flock in Finland. Y. pseudotuberculosis is a quite rare zoonotic bacterium, which typically causes enteritis in humans and sudden death in animals. In this study, osteomyelitis was diagnosed in small, lame, 11- to 12-wk-old male turkeys. Lameness and slower growth among the turkeys was observed on the farm. During pathological examination, multiple lesions were found in the metaphyseal and physeal areas of the femurs, tibiotarsi, and tarsometatarsi, with multifocal to coalescing mixed heterophilic/granulomatous necrotizing osteomyelitis. Y. pseudotuberculosis was isolated from the femoral and tibiotarsal bones or from the joints of six lame turkeys sent for necropsy. The isolation required homogenizing of lesion tissue in phosphate-mannitol-peptone broth, which was cultured directly - and, if needed, after cold enrichment - on selective cefsulodin-irgasan-novobiocin agar. Whole-genome sequencing was used for identification and typing. All isolates belonged to bio/serotype 1/O:1a and sequence type ST42 (Achtman scheme), which is commonly reported in both human and animal Y. pseudotuberculosis infections in Europe. The isolates from all six turkeys showed only one to two allele differences in the core genome comparison, indicating a common source of infection. All asymptomatic turkeys were slaughtered at the age of 17 weeks. Whole and partial carcass condemnation rates at the slaughterhouse were high, but no macroscopic changes in the skeletal system were found, showing that food chain information is essential. This study confirms earlier findings that Y. pseudotuberculosis can cause osteomyelitis in fattening turkeys, leading to lameness. Food chain information is essential for slaughterhouse operations, to protect the workers and emphasize good working hygiene during slaughter.
Topics: Animals; Lameness, Animal; Male; Osteomyelitis; Turkeys; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis Infections
PubMed: 35429816
DOI: 10.1016/j.vetmic.2022.109424 -
Journal of Food Protection Jan 2018Maximum growth temperature and growth limits in Luria-Bertani broth at different pH values and NaCl and ethanol concentrations were determined for 49 Yersinia...
Maximum growth temperature and growth limits in Luria-Bertani broth at different pH values and NaCl and ethanol concentrations were determined for 49 Yersinia pseudotuberculosis strains representing serotypes O:1, O:2, O:3, O:4, and O:5. In addition, the ability of the strains to grow at 0°C and the growth parameters at 1°C were determined. The maximum growth temperatures measured by Gradiplate temperature incubator varied between 42.2 and 43.7°C. All strains were able to grow at 0°C in Luria-Bertani broth within 17 days of incubation. At 1°C, differences were observed among strains in the maximum growth rates and area under the curve values based on optical density data, which suggests that some Y. pseudotuberculosis strains adapt faster to colder conditions. The mean maximum growth rates and area under the curve values at 1°C, as well as the mean maximum growth temperatures, were statistically significantly higher among serotype O:1 strains compared with O:3 strains and among biotype 1 compared with biotype 2 strains. All strains grew at pH 4.5, whereas none of the strains were able to grow at pH 4.2. The highest pH at which growth was observed varied between 9.0 and 9.3. For 14 strains the maximum NaCl concentration at which growth was observed was 4.8%, whereas 35 of the strains were able to grow at 5.0% NaCl. None of the strains showed growth at 5.2% NaCl. All strains were able to grow at 4.5% ethanol concentration (v/v), whereas 5.0% ethanol concentration was completely inhibitory to all strains. The observed limited physiological diversity among various Y. pseudotuberculosis strains may stem from the genetic homogeneity of the species.
Topics: Ethanol; Hydrogen-Ion Concentration; Sodium Chloride; Temperature; Yersinia enterocolitica; Yersinia pseudotuberculosis
PubMed: 29283703
DOI: 10.4315/0362-028X.JFP-17-223 -
Protein Science : a Publication of the... Jun 2017Enteropathogenic Yersinia expresses several invasins that are fundamental virulence factors required for adherence and colonization of tissues in the host. Within the...
Enteropathogenic Yersinia expresses several invasins that are fundamental virulence factors required for adherence and colonization of tissues in the host. Within the invasin-family of Yersinia adhesins, to date only Invasin has been extensively studied at both structural and functional levels. In this work, we structurally characterize the recently identified inverse autotransporter InvasinE from Yersinia pseudotuberculosis (formerly InvasinD from Yersinia pseudotuberculosis strain IP31758) that belongs to the invasin-family of proteins. The sequence of the C-terminal adhesion domain of InvasinE differs significantly from that of other members of the Yersinia invasin-family and its detailed cellular and molecular function remains elusive. In this work, we present the 1.7 Å crystal structure of the adhesion domain of InvasinE along with two Immunoglobulin-like domains. The structure reveals a rod shaped architecture, confirmed by small angle X-ray scattering in solution. The adhesion domain exhibits strong structural similarities to the C-type lectin-like domain of Yersinia pseudotuberculosis Invasin and enteropathogenic/enterohemorrhagic E. coli Intimin. However, despite the overall structural similarity, the C-type lectin-like domain in InvasinE lacks motifs required for Ca /carbohydrate binding as well as sequence or structural features critical for Tir binding in Intimin and β -integrin binding in Invasin, suggesting that InvasinE targets a distinct, yet unidentified molecule on the host-cell surface. Although the biological role and target molecule of InvasinE remain to be elucidated, our structural data provide novel insights into the architecture of invasin-family proteins and a platform for further studies towards unraveling the function of InvasinE in the context of infection and host colonization.
Topics: Adhesins, Bacterial; Amino Acid Motifs; Crystallography, X-Ray; Protein Domains; Yersinia pseudotuberculosis
PubMed: 28370712
DOI: 10.1002/pro.3171 -
Microbiology Spectrum Aug 2022Yersinia pseudotuberculosis is an enteric pathogen causing mild enteritis that can lead to mesenteric adenitis in children and septicemia in elderly patients. Most cases...
Yersinia pseudotuberculosis is an enteric pathogen causing mild enteritis that can lead to mesenteric adenitis in children and septicemia in elderly patients. Most cases are sporadic, but outbreaks have already been described in different countries. We report for the first time a Y. pseudotuberculosis clonal outbreak in France, that occurred in 2020. An epidemiological investigation based on food queries pointed toward the consumption of tomatoes as the suspected source of infection. The National Reference Laboratory (YNRL) developed a new cgMLST scheme with 1,921 genes specific to Y. pseudotuberculosis that identified the clustering of isolates associated with the outbreak and allowed to perform molecular typing in real time. In addition, this method allowed to retrospectively identify isolates belonging to this cluster from earlier in 2020. This method, which does not require specific bioinformatic skills, is now used systematically at the YNRL and proves to display an excellent discriminatory power and is available to the scientific community. We describe in here a novel core-genome MLST method that allowed to identify in real time, and for the first time in France, a Y. pseudotuberculosis clonal outbreak that took place during the summer 2020 in Corsica. Our method allows to support epidemiological and microbiological investigations to establish a link between patients infected with closely associated Y. pseudotuberculosis isolates, and to identify the potential source of infection. In addition, we made this method available for the scientific community.
Topics: Aged; Child; Disease Outbreaks; Humans; Multilocus Sequence Typing; Retrospective Studies; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis Infections
PubMed: 35863020
DOI: 10.1128/spectrum.01145-22 -
BMJ Case Reports Feb 2020is a Gram-negative zoonosis which occasionally infects humans via ingestion of contaminated food and water, and typically causes a self-limiting gastrointestinal tract...
is a Gram-negative zoonosis which occasionally infects humans via ingestion of contaminated food and water, and typically causes a self-limiting gastrointestinal tract infection. Patients who are immunocompromised, have haemochromatosis or liver cirrhosis are more likely to develop serious complications such as bacteraemia. We present the case of a 76-year-old man with fever and an acutely tender, swollen right knee. Blood cultures were positive for , and 16s ribosomal PCR analysis of his knee aspirate confirmed septic arthritis. He was treated with intravenous ceftriaxone and made an excellent recovery following knee washout. Interestingly, our patient did not have any of the classic risk factors described in the literature, or history of exposure to the pathogen to explain his diagnosis. To our knowledge, this is only the second confirmed case of bacteraemia with septic arthritis, and the first to involve the knee joint.
Topics: Aged; Arthritis, Infectious; Bacteremia; Fever; Humans; Knee Joint; Male; Risk Factors; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis Infections
PubMed: 32060113
DOI: 10.1136/bcr-2019-233125 -
PLoS Pathogens May 2022Antibiotic tolerance is typically associated with a phenotypic change within a bacterial population, resulting in a transient decrease in antibiotic susceptibility that...
Antibiotic tolerance is typically associated with a phenotypic change within a bacterial population, resulting in a transient decrease in antibiotic susceptibility that can contribute to treatment failure and recurrent infections. Although tolerant cells may emerge prior to treatment, the stress of prolonged antibiotic exposure can also promote tolerance. Here, we sought to determine how Yersinia pseudotuberculosis responds to doxycycline exposure, to then verify if these gene expression changes could promote doxycycline tolerance in culture and in our mouse model of infection. Only four genes were differentially regulated in response to a physiologically-relevant dose of doxycycline: osmB and ompF were upregulated, tusB and cnfy were downregulated; differential expression also occurred during doxycycline treatment in the mouse. ompF, tusB and cnfy were also differentially regulated in response to chloramphenicol, indicating these could be general responses to ribosomal inhibition. cnfy has previously been associated with persistence and was not a major focus here. We found deletion of the OmpF porin resulted in increased antibiotic accumulation, suggesting expression may promote diffusion of doxycycline out of the cell, while OsmB lipoprotein had a minor impact on antibiotic permeability. Overexpression of tusB significantly impaired bacterial survival in culture and in the mouse, suggesting that tRNA modification by tusB, and the resulting impacts on translational machinery, promotes survival during treatment with an antibiotic classically viewed as bacteriostatic. We believe this may be the first observation of bactericidal activity of doxycycline under physiological conditions, which was revealed by reversing tusB downregulation.
Topics: Animals; Anti-Bacterial Agents; Doxycycline; Mice; Permeability; RNA, Transfer; Yersinia pseudotuberculosis
PubMed: 35576231
DOI: 10.1371/journal.ppat.1010556