CONICET | Buscador de Institutos y Recursos Humanos

C. perfringens is an anaerobic Gram-positive spore-forming bacterium responsible for the production of severe histotoxic and gastrointestinal diseases in humans and animals. In silico analysis of the three available genome-sequenced C. perfringens strains (13, SM101 and ATCC13124) revealed that genes that encode flagellar proteins and genes involved in chemotaxis are absent. However, those strains exhibit Type IV pili-dependent gliding motility. Since carbon catabolite regulation has been implicated in the control of different bacterial behaviors we investigated the effect of glucose and other readily metabolized carbohydrates on C. perfringens gliding motility. Our results demonstrate that carbon catabolite regulation constitutes an important physiological regulatory mechanism that reduces the proficiency of gliding motility of a large number of unrelated human and animal-derived pathogenic C. perfringens strains. Glucose produces a strong dose-dependent inhibition of gliding development without affecting vegetative growth. Maximum gliding inhibition was observed at a glucose concentration (1%) previously reported to also inhibit other important behaviors in C. perfringens, such as spore development. The inhibition of gliding development in the presence of glucose was due, at least in part, to the repression of the genes pilT and pilD, whose products are essential for TFP-dependent gliding proficiency. The inhibitory effect of glucose on pilT and pilD expression was under the control of the key regulatory protein CcpA (catabolite control protein A). The deficiency in CcpA activity of a ccpA knock-out C. perfringens mutant strain restored the expression of pilT and pilD and gliding proficiency in the presence of 1% glucose. Carbon catabolite repression of gliding motility of the ccpA- mutant strain was restored after the introduction of a complementing plasmid harboring a wild type copy of ccpA. These results point to a central role for CcpA in orchestrating the negative effect of carbon catabolite regulation on C. perfringens gliding motility. Furthermore, we discovered a novel positive role, in the absence of catabolite regulation, of CcpA on pilT / pilD expression and gliding proficiency. Carbon catabolite repression of gliding motility and the dual role of CcpA, either as repressor or activator of gliding, are analyzed in the context of the different social behaviors and diseases produced by C. perfringens.