Sugar inhibits the production of the toxins that triggers clostridial gas gangrene

MÉNDEZ MARCELO; GOÑI ANIBAL; RAMIREZ WALTER; GRAU ROBERTO RICARDO

MICROBIAL PATHOGENESIS

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2012 vol. 52 p. 85 - 91

0882-4010

Histotoxic strains of Clostridium perfringens cause human gas gangrene, a devastating infection during which potent tissue-degrading toxins are produced. Although this pathogen only grows in anaerobic-nutrient-rich habitats such as deep wounds, very little is known regarding how nutritional signals influence gas gangrene-related toxin production. We hypothesize that sugars, which have been used throughout history to prevent wound infection, may represent a nutritional signal against gangrene development. Here we demonstrate, for the first time, that sugars (sucrose, glucose) inhibited the production of the main protein toxins, PLC (alpha-toxin) and PFO (theta-toxin), responsible for the onset and progression of gas gangrene. Transcription analysis experiments using plc-gusA and pfoA-gusA reporter fusions as well as RT-PCR analysis of mRNA transcripts confirmed that sugar represses plc and pfoA expression.  In contrast an isogenic C. perfringens strain that is defective in CcpA, the master transcription factor involved in carbon catabolite response, was completely resistant to the sugar-mediated inhibition of PLC and PFO toxin production. Therefore, CcpA is the primary or unique regulatory protein responsible for the carbon catabolite (sugar) repression of toxin production of this pathogen. Furthermore, we report that the production of PLC and PFO toxins in the ccpA mutant strain were several-fold higher than the toxin production found in the wild type strain, suggesting that CcpA plays an important physiological role for the development and aggressiveness of clostridial gas gangrene. The present results are analyzed in the context of the well-known, although poorly understood, anti-infective and wound healing effects of sugars and related substances.