The staphylococcal respiratory response regulator SrrAB induces ica gene transcription and polysaccharide intercellular adhesin expression, protecting Staphylococcus aureus from neutrophil killing under anaerobic growth conditions.
In anaerobic environments, Staphylococcus aureus increases the transcription of the intercellular adhesin (ica) cluster, leading to increased polysaccharide intercellular adhesin (PIA) production. The regulatory mechanisms involved in this phenotypic change are mostly unknown. Here we show that the staphylococcal respiratory response regulator, SrrAB, significantly increases icaA transcription under anaerobic growth in S. aureus. Phosphorylated SrrA preferentially bound to a 100 bp DNA sequence located upstream of ica, and dot blot assays revealed little or no PIA expression in S. aureus srrAB deletion-replacement mutants of strains Sa113 and SH1000, grown anaerobically. The biological relevance of SrrAB for S. aureus was assessed in a phagocytosis assay employing human neutrophils. Sixty-eight per cent of PIA producing wild-type cells, but only 19% of srrAB mutant cells survived under anaerobic conditions, suggesting that PIA protected S. aureus against non-oxidative killing mechanisms of the neutrophils. No protection was observed when S. aureus or S. epidermidis strains, producing PIA also under aerobic conditions, were subjected to phagocytosis under aerobic conditions. These results demonstrate that SrrAB is a major activator of ica expression and PIA production in anaerobic environments, where it contributes to the protection of S. aureus against non-oxidative defence mechanisms.
Ulrich
Martina
M
Institute of Medical Microbiology and Hygiene, Universitätsklinikum Tübingen, Germany.
Bastian
Mike
M
Cramton
Sarah E
SE
Ziegler
Katrin
K
Pragman
Alexa A
AA
Bragonzi
Alessandra
A
Memmi
Guido
G
Wolz
Christiane
C
Schlievert
Patrick M
PM
Cheung
Ambrose
A
Döring
Gerd
G
D000693:Anaerobiosis; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D013212:Staphylococcus epidermidis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D012097:Repressor Proteins; C422459:SrrA protein, Staphyolococcus aureus; C422460:SrrB protein, Staphyolococcus aureus; C113579:polysaccharide intercellular adhesin; D010100:Oxygen