A Novel Role for D-alanylation of Lipoteichoic Acid of Enterococcus Faecalis in Urinary Tract Infection

PLoS One. 2014 Oct 8;9(10):e107827. doi: 10.1371/journal.pone.0107827. eCollection 2014.

Abstract

Background: Enterococci are the third most common cause of healthcare-associated infections, which include urinary tract infections, bacteremia and endocarditis. Cell-surface structures such as lipoteichoic acid (LTA) have been poorly examined in E. faecalis, especially with respect to urinary tract infections (UTIs). The dlt operon is responsible for the D-alanylation of LTA and includes the gene dltA, which encodes the D-alanyl carrier protein ligase (Dcl). The involvement of LTA in UTI infection by E. faecalis has not been studied so far. Here, we examined the role of teichoic acid alanylation in the adhesion of enterococci to uroepithelial cells.

Results: In a mouse model of urinary tract infection, we showed that E. faecalis 12030ΔdltA mutant colonizes uroepithelial surfaces more efficiently than wild type bacteria. We also demonstrated that this mutant adhered four fold better to human bladder carcinoma cell line T24 compared to the wild type strain. Bacterial adherence could be significantly inhibited by purified lipoteichoic acid (LTA) and inhibition was specific.

Conclusion: In contrast to bacteraemia model and adherence to colon surfaces, E. faecalis 12030ΔdltA mutant colonized uroepithelial surfaces more efficiently than wild-type bacteria. In the case of the uroepithelial surface the adherence to specific host cells could be prevented by purified LTA. Our results therefore suggest a novel function of alanylation of LTA in E. faecalis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Adhesion / drug effects
  • Cell Line, Tumor
  • Enterococcus faecalis / drug effects
  • Enterococcus faecalis / metabolism*
  • Enterococcus faecalis / pathogenicity*
  • Female
  • Humans
  • Lipopolysaccharides / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Teichoic Acids / metabolism*
  • Teichoic Acids / pharmacology*
  • Urinary Tract Infections / metabolism*

Substances

  • Lipopolysaccharides
  • Teichoic Acids
  • lipoteichoic acid

Grant support

This work was supported by grants from the German Ministry of Science and Education (BMBF:UroGenOmics0315833C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.