RT Journal Article
T1 Large-scale screening of a targeted Enterococcus faecalis mutant library identifies envelope fitness factors
A1 Rigottier-Gois, Lionel
A1 Alberti, Adriana
A1 Houel, Armel
A1 Taly, Jean-François
A1 Palcy, Philippe
A1 Manson, Janet
A1 Pinto, Daniela
A1 Matos, Renata
A1 Carrilero Aguado, Laura
A1 Montero Serra, Natalia
A1 Tariq, Muhammad
A1 Karsens, Harma
A1 Repp, Christian
A1 Kropec, Andrea
A1 Budin-Verneuil, Aurélie
A1 Benachour, Abdellah
A1 Sauvageot, Nicolas
A1 Bizzini, Alain
A1 Gilmore, Michael
A1 Bessières, Philippe
A1 Kok, Jan
A1 Huebner, Johannes
A1 Lopes, Fatima
A1 Hartke, Axel
A1 Serror, Pascale
A1 González Zorn, Bruno
AB 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.
PB Public Library Science
SN 1932-6203
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/45174
UL https://hdl.handle.net/20.500.14352/45174
LA eng
NO Unión Europea. FP6
NO Ministerio de Ciencia e Innovación (MICINN)
NO Agence Nationale de la Recherche
NO Fundaçaõ para a Ciência e Tecnologia
DS Docta Complutense
RD 10 abr 2025