Biology subjects

Demeure, C. E.

Publications and source records attributed to Demeure, C. E..

4 recordsLinked to original sources

bioRxiv2026

Yersinia pestis lipoprotein SlyB promotes plague pathogenesis via envelope stress tolerance

Yersinia pestis, the etiological agent of plague, persists in an enzootic cycle involving mammals and fleas, requiring constant outer membrane (OM) adaptation to disparate host environments. One such pathway involves the glycine zipper 2TM domain-containing protein SlyB, a central component of the OM stress response and PhoPQ virulence pathway. While the OM is critical for virulence, the role of the OM lipoprotein SlyB in Y. pestis ecology and pathogenesis remains unknown. We show by phylogenetic analyses that slyB paralogs expanded in environmental bacteria, whereas the canonical slyB gene was under negative selective pressure during Y. pestis speciation from Yersinia pseudotuberculosis. Using rodent and flea infection models recapitulating Y. pestis natural history, we demonstrate that SlyB is specifically required to resist the mammalian immune system at 37{degrees}C, including neutrophil-mediated antimicrobial activity during lymph node colonization, but is dispensable in septicemic plague in rodents. Strikingly, SlyB is not required for flea colonization and resistance to the antimicrobial-peptide-based immunity of arthropods at lower temperatures. SlyB-dependent OM stress tolerance reveals a mechanism by which Y. pestis establishes bubonic plague, in line with its critical lipopolysaccharide structural switch. Our findings identify SlyB as an evolutionarily fine-tuned component of the Y. pestis envelope that mediates immune escape upon infection of mammalian hosts through maintenance of structural integrity.

microbiology↗

bioRxiv2024

Contribution of the Type 3 Secretion System to immunogenicity of a live Yersinia pseudotuberculosis plague vaccine

The causative agent of plague, Yersinia pestis, remains a treat for public health worldwide. In the perspective to develop effective and safe vaccines, we present here a derived version of our Y. pseudotuberculosis VTnF1 live attenuated vaccine candidate that lacks the pYV virulence plasmid coding for the Type 3 Secretion system (T3SS) and no antibiotic resistance cassettes. This strain, called VpYV-, was safe for immunodeficient mice, and thus can be considered as deeply attenuated. It still has tropism for lymphatic tissues (Peyers patches, Mesenteric lymph nodes) but hardly reaches the spleen and liver. It elicits IgG to the F1 antigen as efficiently as VTnF1 but less directed to other Yersinia antigens. A single oral dose induced 100% protection against bubonic and pneumonic forms of plague, but this protection decreased faster with time than that of VTnF1. In the same line, VpYV-was 30% less protective against a F1-negative Y. pestis, revealing that the tools encoded by pYV are mandatory to obtain a large spectrum protection. Finally, VTnF1 like the Y. pestis vaccine EV76 can induce protection against co-infected Y. pestis relying on host iron nutritional immunity", indicating a potential use as therapeutics of recent infection. In contrast VpYV-failed to do so, revealing an importance of the T3SS in this mechanism. Overall, VpYV- and its parental strain VTnF1 offer a choice between more attenuation and safety or vaccine performances. They give an alternative and may represent useful tools to prevent and treat Y. pestis infection in healthy or immunosuppressed individuals.

microbiology↗

bioRxiv2023

Reply to Barton et al: signatures of natural selection during the Black Death

Barton et al.1 raise several statistical concerns regarding our original analyses2 that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high FST values at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant near ERAP2 continues to emerge as the strongest candidate for selection (p = 1.2x10-5), falling below the Bonferroni-corrected significance threshold recommended by Barton et al. Importantly, the evidence for selection on ERAP2 is further supported by functional data demonstrating the impact of the ERAP2 genotype on the immune response to Y. pestis and by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.

genomics↗

bioRxiv2019

Subcutaneous vaccination with a live attenuated Yersinia pseudotuberculosis plague vaccine

A single oral inoculation to mice of the live attenuated Yersinia pseudotuberculosis VTnF1 strain producing an F1 pseudocapsule protects against bubonic and pneumonic plague. However oral vaccination can fail in humans exposed to frequent intestinal infections. We evaluated in mice the efficacy of subcutaneous vaccine injection as an alternative way to induce protective immunity, while reducing the dose and avoiding strain release in nature. A single subcutaneous dose of up to 108 CFU induced dose-dependent antibody production. At the dose of 107 CFU, i.e. 10 times less than via the oral route, it caused a modest skin reaction and protected 100% against bubonic and 80% against pneumonic plague, caused by high doses of Yersinia pestis. Bacteria migrating to lymph nodes and spleen, but not feces, were rapidly eliminated. Thus, subcutaneous injection of VTnF1 would represent a good alternative when dissemination in nature and human intestinal responsiveness are limitations.

immunology↗