Biology subjects

Carniel, E.

Publications and source records attributed to Carniel, E..

4 recordsLinked to original sources

bioRxiv2024

Global evolutionary patterns of Yersinia pestis and its spread into Africa

The zoonotic pathogen Yersinia pestis, the etiologic agent of plague, has caused three major pandemics and diversified in different lineages currently established in endemic areas worldwide1-3. However, some regions like continental Africa have been poorly covered within the global diversity and epidemiological history of this pathogen2,4-6. Here, we report the whole-genome sequences of 1,124 Y. pestis isolates collected from endemic areas worldwide over 116 years, nearly doubling the available genomic data for the species. By integrating population genomics and historical research, we retrace the introduction of multiple Y. pestis lineages into continental Africa, revealing the diversity of the 1.ANT lineage, its historical emergence and its spread to and within Africa since the late 17th century. We identify key mechanisms of genome evolution, including signatures of adaptive evolution present in virulence and biofilm-related genes such as RovA, a master virulence regulator, which likely play a role in the pathogens adaptation and endemic persistence. Additionally, our findings reveal an increased trajectory of genome degradation and expansion of IS elements in different lineages. This trend appears especially pronounced in 1.ANT genomes, promoting the remarkable genomic variation within this lineage. Taken together, our findings shed light on the introduction and evolutionary history of plague in Africa and provide a comprehensive framework for understanding the global diversity and genome evolution of Y. pestis, revealing potential factors contributing to its long-term adaptation in endemic areas.

microbiology↗

bioRxiv2024

In-host evolution of Yersinia enterocolitica during a chronic human infection

Following a pacemaker implantation, a 75-years-old patient suffered from five successive bacteremia episodes between in 1999 and 2013 despite long-term antibiotic treatment, with intermittent vegetation apparition on the device atrial lead. Four blood isolates, identified as Yersinia enterocolitica bioserotype 4/O:3, were further genetically and phenotypically characterized. Phylogenetic reconstruction showed that the patient was chronically infected by the same strain, which evolved within the host for 14 years. Single-nucleotide polymorphism (SNP) analysis indicates that the last two isolates evolved in parallel and formed two independent lineages within the host. Pan-genome analysis and genome comparison showed that their common evolution was characterized by 41 small insertion/deletion events, loss of three large DNA fragments and mutations in 140 genes. A phylogenetic analysis by maximum likelihood identified two genes presenting a positive selection signal, suggesting that these mutations provided a survival advantage to bacteria during chronic infection. Quinolone resistance in the last two isolates was acquired through a so far undescribed deletion in the gyrA gene. Mass-spectrometry analysis revealed a strong proteome remodeling in the last two isolates which was correlated with a truncation in the stringent response regulator DksA. A reduced carbon, energy and purine metabolism supports their severe growth defects in vitro. 3rd-generation cephalosporin resistance of the last isolate was correlated with a truncation of OmpF, the main porin translocating antibiotics through the outer-membrane, as well as an increased production of BlaA and AmpC {beta}-lactamases. This is the first report of genetic and phenotypic changes associated to within-host adaptation of a pathogenic Yersinia species under antibiotic pressure.

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↗

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↗