| Title: | "Multiple roles for Enterococcus faecalis glycosyltransferases in biofilm-associated antibiotic resistance, cell envelope integrity, and conjugative transfer" |
| Author(s): | Dale JL; Cagnazzo J; Phan CQ; Barnes AM; Dunny GM; |
| Address: | "Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA. Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA dunny001@umn.edu" |
| Journal Title: | Antimicrob Agents Chemother |
| ISSN/ISBN: | 1098-6596 (Electronic) 0066-4804 (Print) 0066-4804 (Linking) |
| Abstract: | "The emergence of multidrug-resistant bacteria and the limited availability of new antibiotics are of increasing clinical concern. A compounding factor is the ability of microorganisms to form biofilms (communities of cells encased in a protective extracellular matrix) that are intrinsically resistant to antibiotics. Enterococcus faecalis is an opportunistic pathogen that readily forms biofilms and also has the propensity to acquire resistance determinants via horizontal gene transfer. There is intense interest in the genetic basis for intrinsic and acquired antibiotic resistance in E. faecalis, since clinical isolates exhibiting resistance to multiple antibiotics are not uncommon. We performed a genetic screen using a library of transposon (Tn) mutants to identify E. faecalis biofilm-associated antibiotic resistance determinants. Five Tn mutants formed wild-type biofilms in the absence of antibiotics but produced decreased biofilm biomass in the presence of antibiotic concentrations that were subinhibitory to the parent strain. Genetic determinants responsible for biofilm-associated antibiotic resistance include components of the quorum-sensing system (fsrA, fsrC, and gelE) and two glycosyltransferase (GTF) genes (epaI and epaOX). We also found that the GTFs play additional roles in E. faecalis resistance to detergent and bile salts, maintenance of cell envelope integrity, determination of cell shape, polysaccharide composition, and conjugative transfer of the pheromone-inducible plasmid pCF10. The epaOX gene is located in a variable extended region of the enterococcal polysaccharide antigen (epa) locus. These data illustrate the importance of GTFs in E. faecalis adaptation to diverse growth conditions and suggest new targets for antimicrobial design" |
| Keywords: | "Anti-Bacterial Agents/*pharmacology Bile Acids and Salts/pharmacology Biofilms/*drug effects Cell Wall/genetics Conjugation, Genetic DNA Transposable Elements/genetics Detergents/pharmacology Drug Resistance, Bacterial/*genetics Drug Resistance, Multiple, ;" |
| Notes: | "MedlineDale, Jennifer L Cagnazzo, Julian Phan, Chi Q Barnes, Aaron M T Dunny, Gary M eng R56 AI058134/AI/NIAID NIH HHS/ T90 DE022732/DE/NIDCR NIH HHS/ AI058134/AI/NIAID NIH HHS/ T32 HL007741/HL/NHLBI NIH HHS/ T90 DE0227232/DE/NIDCR NIH HHS/ R01 AI058134/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural 2015/04/29 Antimicrob Agents Chemother. 2015 Jul; 59(7):4094-105. doi: 10.1128/AAC.00344-15. Epub 2015 Apr 27" |
