Role of RegM, a homologue of the catabolite repressor protein CcpA, in the virulence of XXXX .

@entity3363 @entity7969 @entity7791 @entity19 @entity2260 @entity2348 @entity1132 @entity969 @entity3649 @entity505 @entity20485 @entity328 @entity413
As part of a study of virulence gene regulation in @entity328 , we have identified a gene encoding a homologue of the staphylococcal catabolite control protein CcpA in the pneumococcal genome sequence. The pneumococcal protein, designated RegM, has significant similarity to members of the LacI/GalR family of @entity2348 . @entity20485 derivatives with insertion-duplication or deletion mutations in regM were significantly attenuated in virulence with respect to the wild-type strain. In defined media containing either @entity969 or @entity1132 as sole @entity505 sources, the in vitro growth rates of @entity20485 and the regM mutants were essentially the same. However, in the presence of @entity3649 the regM mutants grew significantly faster than the wild-type strain, whereas growth rates were significantly lower in the presence of @entity413 or @entity7969 . These data are consistent with the involvement of regM in the catabolism of @entity3363 in @entity2260 . RegM was a repressor of both @entity7791 activities in @entity2260 , but unlike the situation in certain other bacteria, it does not mediate the repression of these enzymes by @entity413 . The observed attenuation in virulence was not attributable to poorer growth of the regM mutants in @entity19 blood ex vivo, but nevertheless, the mutants were rapidly cleared from the blood of infected @entity19 in vivo. The regM mutation had no apparent impact on expression of several confirmed pneumococcal virulence proteins, but studies employing a lacZ transcriptional fusion construct indicated that mutation of regM resulted in a significant reduction in transcription of the capsular polysaccharide biosynthesis locus (cps). Thus, regM is the first gene outside of the cps locus to be implicated in regulation of capsular gene expression.
