Large-scale screening of a targeted Enterococcus faecalis mutant library identifies envelope fitness factors



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Rigottier-Gois, Lionel and Alberti, Adriana and Houel, Armel and Taly, Jean-François and Palcy, Philippe and Manson, Janet and Pinto, Daniela and Matos, Renata C and Carrilero Aguado, Laura and Montero Serra, Natalia and Tariq, Muhammad and Karsens, Harma and Repp, Christian and Kropec, Andrea and Budin-Verneuil, Aurélie and Benachour, Abdellah and Sauvageot, Nicolas and Bizzini, Alain and Gilmore, Michael S and Bessières, Philippe and Kok, Jan and Huebner, Johannes and Lopes, Fatima and Gonzalez Zorn, Bruno and Hartke, Axel and Serror, Pascale (2011) Large-scale screening of a targeted Enterococcus faecalis mutant library identifies envelope fitness factors. PLoS ONE, 6 (12). e29023. ISSN 1932-6203

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Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence.

Item Type:Article
Subjects:Medical sciences > Veterinary
ID Code:39674
Deposited On:22 Dec 2016 09:24
Last Modified:05 Apr 2022 07:42

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