Microdiversity of Enterococcus faecalis isolates in cases of infective endocarditis: selection of non-synonymous mutations and large deletions is associated with phenotypic modifications
| Autor: | Raphaël Lepeule, Paul-Louis Woerther, Christophe Rodriguez, Guilhem Royer, P. Lim, Lolita Roisin, S. Lo, Jean-Michel Pawlotsky, L. Coutte, Hervé Jacquier, Vanessa Demontant |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Epidemiology 030106 microbiology Immunology Context (language use) Microbiology Enterococcus faecalis 03 medical and health sciences Virology Drug Discovery medicine Humans Gram-Positive Bacterial Infections Selection (genetic algorithm) Aged Sequence Deletion Aged 80 and over Whole genome sequencing Genetics whole genome sequencing biology infective endocarditis Genetic Variation Endocarditis Bacterial General Medicine medicine.disease biology.organism_classification Heart Valves Phenotype 030104 developmental biology Infectious Diseases microdiversity Codon Nonsense Infective endocarditis Female Parasitology Genome Bacterial Non synonymous Research Article |
| Zdroj: | Emerging Microbes & Infections article-version (VoR) Version of Record |
| ISSN: | 2222-1751 |
| DOI: | 10.1080/22221751.2021.1924865 |
| Popis: | Context: Today, infective endocarditis (IE) caused by Enterococcus faecalis represents 10% of all IE and is marked by its difficult management and the frequency of relapses. Although the precise reasons for that remain to be elucidated, the evolution of the culprit strain under selective pressure through microdiversification could be, at least in part, involved. Material and methods: To further study the in situ genetic microdiversity and its possible phenotypic manifestations in E. faecalis IE, we sequenced and compared multiple isolates from the valves, blood culture and joint fluid of five patients who underwent valvular surgery. Growth rate and early biofilm production of selected isolates were also compared. Results: By sequencing a total of 58 E. faecalis genomes, we detected a considerable genomic microdiversity, not only among strains from different anatomical origins, but also between isolates from the same studied cardiac valves. Interestingly, deletions of thousands of bases including the well-known virulence factors ebpA/B/C, and srtC, as well as other large prophage sequences containing genes coding for proteins implicated in platelet binding (PlbA and PlbB) were evidenced. The study of mutations helped unveil common patterns in genes related to the cell cycle as well as central metabolism, suggesting an evolutionary convergence in these isolates. As expected, such modifications were associated with a significant impact on the in-vitro phenotypic heterogeneity, growth, and early biofilm production. Conclusion: Genome modifications associated with phenotypic variations may allow bacterial adaptation to both antibiotic and immune selective pressures, and thus promote relapses. |
| Databáze: | OpenAIRE |
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