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


Autoria(s): Rigottier-Gois, Lionel; Alberti, Adriana; Houel, Armel; Taly, Jean-François; Palcy, Philippe; Manson, Janet; Pinto, Daniela; Matos, Renata C; Carrilero Aguado, Laura; Montero Serra, Natalia; Tariq, Muhammad; Karsens, Harma; Repp, Christian; Kropec, Andrea; Budin-Verneuil, Aurélie; Benachour, Abdellah; Sauvageot, Nicolas; Bizzini, Alain; Gilmore, Michael S; Bessières, Philippe; Kok, Jan; Huebner, Johannes; Lopes, Fatima; Gonzalez Zorn, Bruno; Hartke, Axel; Serror, Pascale
Data(s)

2011

Resumo

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.

Formato

application/pdf

Identificador

http://eprints.ucm.es/39674/1/486.pdf

Idioma(s)

en

Publicador

Public Library Science

Relação

http://eprints.ucm.es/39674/

http://dx.doi.org/10.1371/journal.pone.0029023

10.1371/journal.pone.0029023

GEN2006-27767-E/ PAT

ANR-06-PATHO-008

0313933

ERA-PTG/0001/2006 and PEst-OE/EQB/LA0004/2011

Direitos

cc_by

info:eu-repo/semantics/openAccess

Palavras-Chave #Veterinaria
Tipo

info:eu-repo/semantics/article

PeerReviewed