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.
