Role of a cysteine synthase in Staphylococcus aureus.
The gram-positive human pathogen Staphylococcus aureus is often isolated with media containing potassium tellurite, to which it has a higher level of resistance than Escherichia coli. The S. aureus cysM gene was isolated in a screen for genes that would increase the level of tellurite resistance of E. coli DH5alpha. The protein encoded by S. aureus cysM is sequentially and functionally homologous to the O-acetylserine (thiol)-lyase B family of cysteine synthase proteins. An S. aureus cysM knockout mutant grows poorly in cysteine-limiting conditions, and analysis of the thiol content in cell extracts showed that the cysM mutant produced significantly less cysteine than wild-type S. aureus SH1000. S. aureus SH1000 cannot use sulfate, sulfite, or sulfonates as the source of sulfur in cysteine biosynthesis, which is explained by the absence of genes required for the uptake and reduction of these compounds in the S. aureus genome. S. aureus SH1000, however, can utilize thiosulfate, sulfide, or glutathione as the sole source of sulfur. Mutation of cysM caused increased sensitivity of S. aureus to tellurite, hydrogen peroxide, acid, and diamide and also significantly reduced the ability of S. aureus to recover from starvation in amino acid- or phosphate-limiting conditions, indicating a role for cysteine in the S. aureus stress response and survival mechanisms.
Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom.
James K
JK
Lithgow
Emma J
EJ
Hayhurst
Gerald
G
Cohen
Yair
Y
Aharonowitz
Simon J
SJ
Foster
D003470:Culture Media; D003545:Cysteine / Q000378:metabolism; D003547:Cysteine Synthase / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D018869:Heat-Shock Response; D006801:Humans; D009154:Mutation; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D013455:Sulfur / Q000378:metabolism; D013691:Tellurium / Q000494:pharmacology
D003470:Culture Media; D013455:Sulfur; D003547:Cysteine Synthase; C026660:tellurous acid; D003545:Cysteine; D013691:Tellurium