Deletion of hypothetical wall teichoic acid ligases in Staphylococcus aureus activates the cell wall stress response.
The Staphylococcus aureus cell wall stress stimulon (CWSS) is activated by cell envelope-targeting antibiotics or depletion of essential cell wall biosynthesis enzymes. The functionally uncharacterized S. aureus LytR-CpsA-Psr (LCP) proteins, MsrR, SA0908 and SA2103, all belong to the CWSS. Although not essential, deletion of all three LCP proteins severely impairs cell division. We show here that VraSR-dependent CWSS expression was up to 250-fold higher in single, double and triple LCP mutants than in wild type S. aureus in the absence of external stress. The LCP triple mutant was virtually depleted of wall teichoic acids (WTA), which could be restored to different degrees by any of the single LCP proteins. Subinhibitory concentrations of tunicamycin, which inhibits the first WTA synthesis enzyme TarO (TagO), could partially complement the severe growth defect of the LCP triple mutant. Both of the latter findings support a role for S. aureus LCP proteins in late WTA synthesis, as in Bacillus subtilis where LCP proteins were recently proposed to transfer WTA from lipid carriers to the cell wall peptidoglycan. Intrinsic activation of the CWSS upon LCP deletion and the fact that LCP proteins were essential for WTA-loading of the cell wall, highlight their important role(s) in S. aureus cell envelope biogenesis.
Institute of Medical Microbiology, University of Zurich, Zürich, Switzerland. vdengler@imm.uzh.ch
Vanina
V
Dengler
Patricia Stutzmann
PS
Meier
Ronald
R
Heusser
Peter
P
Kupferschmied
Judit
J
Fazekas
Sarah
S
Friebe
Sibylle Burger
SB
Staufer
Paul A
PA
Majcherczyk
Philippe
P
Moreillon
Brigitte
B
Berger-Bächi
Nadine
N
McCallum
D001414:Bacitracin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media / Q000378:metabolism; D017353:Gene Deletion; D050939:Gene Fusion; D005798:Genes, Bacterial; D017930:Genes, Reporter; D005816:Genetic Complementation Test / Q000379:methods; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011401:Promoter Regions, Genetic; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D013312:Stress, Physiological; D013682:Teichoic Acids / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
D001426:Bacterial Proteins; D003470:Culture Media; C093500:LytR protein, Staphylococcus aureus; D008565:Membrane Proteins; C477297:MsrR protein, Staphylococcus aureus; D013682:Teichoic Acids; D014157:Transcription Factors; C478169:VraS protein, Staphylococcus aureus; D014415:Tunicamycin; D001414:Bacitracin; D008025:Ligases