CymR, the master regulator of cysteine metabolism in Staphylococcus aureus, controls host sulphur source utilization and plays a role in biofilm formation.
We have characterized the master regulator of cysteine metabolism, CymR, in Staphylococcus aureus. CymR repressed the transcription of genes involved in pathways leading to cysteine formation. Eight direct DNA targets were identified using gel-shift or footprinting experiments. Comparative transcriptome analysis and in vitro studies indicated that CysM, the OAS-thiol-lyase, was also implicated in this regulatory system. OAS, the direct precursor of cysteine, prevents CymR-dependent binding to DNA. This study has allowed us to predict sulphur metabolism functions for previously uncharacterized S. aureus genes. We show that S. aureus is able to grow on homocysteine as the sole sulphur source suggesting efficient MccA and MccB-dependent conversion of this compound into cysteine. We propose that SA1850 is a new thiosulphate transporter and that TcyP and TcyABC are l-cystine transporters. CymR directly controls the use of sulphur sources of human origin such as taurine and homocysteine. The cymR mutant also displayed a reduced capacity to form biofilms, indicating that CymR is involved in controlling this process in S. aureus via an ica-independent mechanism. These data indicate that fine-tuning of sulphur metabolism plays an important part in the physiology of this major pathogen and its adaptation to environmental conditions and survival in the host.
Soutourina
Olga
O
Unité de Génétique des Génomes Bactériens, CNRS URA 2171, France. olga.soutourina@pasteur.fr
Poupel
Olivier
O
Coppée
Jean-Yves
JY
Danchin
Antoine
A
Msadek
Tarek
T
Martin-Verstraete
Isabelle
I
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms; D003553:Cystine / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D012329:RNA, Bacterial / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*
D001426:Bacterial Proteins; D012329:RNA, Bacterial; D012097:Repressor Proteins; D003553:Cystine; D013455:Sulfur