A Staphylococcus aureus ypfP mutant with strongly reduced lipoteichoic acid (LTA) content: LTA governs bacterial surface properties and autolysin activity

Abstract

SummaryMany Gram-positive bacteria produce lipoteichoic acid (LTA) polymers whose physiological roles have remained a matter of debate because of the lack of LTA-deficient mutants. The ypfP gene responsible for biosynthesis of a glycolipid found in LTA was deleted in Staphylococcus aureus SA113, causing 87% reduction of the LTA content. Mass spectrometry and nuclear magnetic resonance spectroscopy revealed that the mutant LTA contained a diacylglycerol anchor instead of the glycolipid, whereas the remaining part was similar to the wild-type polymer except that it was shorter. The LTA mutant strain revealed no major changes in patterns of cell wall proteins or autolytic enzymes compared with the parental strain indicating that LTA may be less important in S. aureus protein attachment than previously thought. However, the autolytic activity of the mutant was strongly reduced demonstrating a role of LTA in controlling autolysin activity. Moreover, the hydrophobicity of the LTA mutant was altered and its ability to form biofilms on plastic was completely abrogated indicating a profound impact of LTA on physicochemical properties of bacterial surfaces. We propose to consider LTA and its biosynthetic enzymes as targets for new antibiofilm strategies.

Lipoteichoic Acids, Phosphate-Containing Polymers in the Envelope of Gram-Positive Bacteria

“…Analysis of pgcA, gtaB, and ypfP mutations in S. aureus corroborated this model (63). Importantly, pgcA, gtaB, and ypfP mutants continue to synthesize poly-(Gro-P); however, LTA is tethered to the membrane via a terminal DAG, instead of Glc 2 -DAG (63,75,76). In staphylococci, ypfP is located in an operon with a second gene, ltaA, which is conserved in several Firmicutes species (63).…”

“…In B. subtilis, UgtP (YpfP) has been shown to inhibit FtsZ assembly (106). ypfP is dispensable for LTA synthesis, as S. aureus ypfP mutants anchor the polymer onto DAG, instead of Glc 2 -DAG; nevertheless, LTA production is greatly reduced in ltaS mutants (63,75,76).…”

Molecular Control of Bacterial Death and Lysis

“…However, their primary function appears to be in the intrinsic control of murein hydrolases produced during normal cell metabolism (63,176). This is achieved by acting as both targets of murein hydrolase binding as well as regulators of their activity.…”

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

“…Lipoteichoic acids (LTAs) are glycerol phosphate polymers linked to a glycolipid terminus in the cytoplasmic membrane (186). The functions of WTAs and LTAs are still being elucidated, with the recent generation of defined mutants, strains producing reduced amounts of teichoic acids, and strains producing altered teichoic acids providing significant insight into their functional roles (68,78,163,248,377,381). It appears that many teichoic acid functions may be nonessential and may possibly involve indirect interactions with other cell wall components (379); however, the complete loss of LTA leads to cell death in S. aureus (104).…”