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Infection and Immunity, June 2006, p. 3651-3656, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.02090-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inorganic Phosphate Induces Spore Morphogenesis and Enterotoxin Production in the Intestinal Pathogen Clostridium perfringens

Valeria A. Philippe,1 Marcelo B. Méndez,1 I-Hsiu Huang,2,3 Lelia M. Orsaria,1 Mahfuzur R. Sarker,2,3 and Roberto R. Grau1*

Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario-Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Rosario, Argentina,1 Department of Microbiology, College of Science,2 Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon3

Received 28 December 2005/ Returned for modification 6 February 2006/ Accepted 27 February 2006

Clostridium perfringens enterotoxin (CPE) is an important virulence factor for food poisoning and non-food borne gastrointestinal (GI) diseases. Although CPE production is strongly regulated by sporulation, the nature of the signal(s) triggering sporulation remains unknown. Here, we demonstrated that inorganic phosphate (Pi), and not pH, constitutes an environmental signal inducing sporulation and CPE synthesis. In the absence of Pi-supplementation, C. perfringens displayed a spo0A phenotype, i.e., absence of polar septation and DNA partitioning in cells that reached the stationary phase of growth. These results received support from our Northern blot analyses which demonstrated that Pi was able to counteract the inhibitory effect of glucose at the onset of sporulation and induced spo0A expression, indicating that Pi acts as a key signal triggering spore morphogenesis. In addition to being the first study reporting the nature of a physiological signal triggering sporulation in clostridia, these findings have relevance for the development of antisporulation drugs to prevent or treat CPE-mediated GI diseases in humans.

* Corresponding author. Mailing address: Facultad de Ciencias Bioquímicas y Farmacéuticas, Departamento de Microbiología, Suipacha 531, Rosario 2000, Argentina. Phone: 54 341 4353377. Fax: 54 341 4390465. E-mail: robertograu{at}fulbrightweb.org.

Editor: J. T. Barbieri

Infection and Immunity, June 2006, p. 3651-3656, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.02090-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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