Involvement of Chromosomally Encoded Homologs of the RRNPP Protein Family in Enterococcus faecalis Biofilm Formation and Urinary Tract Infection Pathogenesis

Abstract
Enterococcus faecalis is an opportunistic pathogen capable of causing infections, including endocarditis and urinary tract infections (UTI). One of the well-characterized quorum-sensing pathways in E. faecalis involves coordination of the conjugal transfer of pheromone-responsive plasmids by PrgX, a member of the RRNPP protein family. Members of this protein family in various Firmicutes have also been shown to contribute to numerous cellular processes, including sporulation, competence, conjugation, nutrient sensing, biofilm formation, and virulence. As PrgX is a plasmid-encoded RRNPP family member, we surveyed the genome of the multidrug-resistant strain V583 for additional RRNPP homologs using computational searches and refined those identified hits for predicted structural similarities to known RRNPP family members. This led us to investigate the contribution of the chromosomally encoded RRNPP homologs to biofilm processes and pathogenesis in a catheter-associated urinary tract infection (CAUTI) model. In this study, we identified five such homologs and report that 3 of the 5 homologs, EF0073, EF1599, and EF1316, affect biofilm formation as well as outcomes in the CAUTI model. IMPORTANCE Enterococcus faecalis causes health care-associated infections and displays resistance to a variety of broad-spectrum antibiotics by acquisition of resistance traits as well as the ability to form biofilms. Even though a growing number of factors related to biofilm formation have been identified, mechanisms that contribute to biofilm formation are still largely unknown. Members of the RRNPP protein family regulate a diverse set of biological reactions in low-G+C Gram-positive bacteria (Firmicutes). Here, we identify three predicted structural homologs of the RRNPP family, EF0073, EF1599, and EF1316, which affect biofilm formation and CAUTI pathogenesis.
Funding Information
  • HHS | National Institutes of Health (AI77782)
  • HHS | National Institutes of Health (AI117424)
  • HHS | National Institutes of Health (R25GM060182)
  • HHS | National Institutes of Health (K12GM063651)
  • National Science Foundation (DBI-1156856)

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