21131496

not annotated - annotated - LINNAEUS only

Staphylococcus aureus ClpC divergently regulates capsule via sae and codY in strain newman but activates capsule via codY in strain UAMS-1 and in strain Newman with repaired saeS.

ClpC is an ATPase chaperone found in most Gram-positive low-GC bacteria. It has been recently reported that ClpC affected virulence gene expression in Staphylococcus aureus. Here we report that ClpC regulates transcription of the cap operon and accumulation of capsule, a major virulence factor for S. aureus. As virulence genes are regulated by a complex regulatory network in S. aureus, we have used capsule as a model to understand this regulation. By microarray analyses of strain Newman, we found that ClpC strongly activates transcription of the sae operon, whose products are known to negatively regulate capsule synthesis in this strain. Further studies indicated that ClpC repressed capsule production by activating the sae operon in strain Newman. Interestingly, the clpC gene cloned into a multiple-copy plasmid vector exhibited an activation phenotype, suggesting that ClpC overexpression has a net positive effect. In the absence of sae function, by either deletion or correction of a native mutation within saeS, we found that ClpC had a positive effect on capsule production. Indeed, in the UAMS-1 strain, which does not have the saeS mutation, ClpC functioned as an activator of capsule production. Our microarray analyses of strain Newman also revealed that CodY, a repressor of capsule production, was repressed by ClpC. Using genetic approaches, we showed that CodY functioned downstream of ClpC, leading to capsule activation both in Newman and in UAMS-1. Thus, ClpC functions in two opposite pathways in capsule regulation in strain Newman but functions as a positive activator in strain UAMS-1.



Ann file

T1	Species 0 21	Staphylococcus aureus

N1 Reference T1 Taxonomy:1280

T2 Species 84 90 newman

N2 Reference T2 Taxonomy:1280

T3 Species 132 138 UAMS-1

N3 Reference T3 Taxonomy:1280

T4 Species 153 159 Newman

N4 Reference T4 Taxonomy:1280

T5 Species 333 354 Staphylococcus aureus

N5 Reference T5 Taxonomy:1280

T6 Species 481 490 S. aureus

N6 Reference T6 Taxonomy:1280

T7 Species 560 569 S. aureus

N7 Reference T7 Taxonomy:1280

T8 Species 667 673 Newman

N8 Reference T8 Taxonomy:1280

T9 Species 932 938 Newman

N9 Reference T9 Taxonomy:1280

T10 Species 1288 1294 UAMS-1

N10 Reference T10 Taxonomy:1280

T11 Species 1431 1437 Newman

N11 Reference T11 Taxonomy:1280

T12 Species 1636 1642 Newman

N12 Reference T12 Taxonomy:1280

T13 Species 1650 1656 UAMS-1

N13 Reference T13 Taxonomy:1280

T14 Species 1736 1742 Newman

N14 Reference T14 Taxonomy:1280

T15 Species 1791 1797 UAMS-1

N15 Reference T15 Taxonomy:1280

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