PLoS ONE publish this investigation article

December 15^th, 2011

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

Rigottier-Gois L., Alberti A., Houel A., Taly JF., Palcy P., Manson J., Pinto D., Matos RC., Carrilero L., Montero N., Tariq M., Karsens H., Repp C., Kropec A., Budin-Verneuil A., Benachour A., Sauvageot N., Bizzini A., Gilmore MS., Bessieres P., Kok J., Huebner J., Lopes F., Gonzalez-Zorn B., Hartke A. and Serror P.

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

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

	Servicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).
	Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM).
	Instituto Nacional de Investigación Agronómica de Francia (INRA).
	Institut des Sciences et Industries du Vivant et de L´environnement (AgroParisTech).
	Department of Microbiology. Harvard Medical School (HMS).
	Department of Molecular Genetics. Harvard Medical School (HMS).
	Department of Ophthalmology. Harvard Medical School (HMS).
	Molecular Genetics. Centre for Life Sciences. University of Groningen.
	Instituto de Biología Experimental Tecnológica (IBET).
	Division of Infectious Diseases. University Medical Center Freiburg.
	Université de Caen (UNICAEN).
	Instituto de Tecnologia Química e Biológica (ITQB). Universidade Nova de Lisboa (UNL).