Clostridium perfringens is ubiquitous in nature and is often found as a commensal of the human and animal gastrointestinal tract. It is the primary etiological agent of clostridial myonecrosis, or
gas gangrene, a serious
infection that results in extensive tissue
necrosis due to the action of one or more potent extracellular toxins. α-toxin and
perfringolysin O are the major extracellular toxins involved in the pathogenesis of
gas gangrene, but histotoxic strains of C. perfringens, such as strain 13, also produce many degradative
enzymes such as
collagenases, hyaluronidases, sialidases and the
cysteine protease, α-
clostripain. The production of many of these toxins is regulated either directly or indirectly by the global VirSR two-component signal transduction system. By isolating a chromosomal mutant and carrying out microarray analysis we have identified an orphan
sensor histidine kinase, which we have named ReeS (regulator of extracellular
enzymes sensor). Expression of the
sialidase genes nanI and nanJ was down-regulated in a reeS mutant. Since complementation with the wild-type reeS gene restored nanI and nanJ expression to wild-type levels, as shown by quantitative reverse transcription-PCR and
sialidase assays we concluded that ReeS positively regulates the expression of these
sialidase genes. However, mutation of the reeS gene had no significant effect on virulence in the mouse myonecrosis model.
Sialidase production in C. perfringens has been previously shown to be regulated by both the VirSR system and RevR. In this report, we have analyzed a previously unknown
sensor histidine kinase, ReeS, and have shown that it also is involved in controlling the expression of
sialidase genes, adding further complexity to the regulatory network that controls
sialidase production in C. perfringens.