Vibrio cholerae cytolysin is essential for high enterotoxicity and apoptosis induction produced by a cholera toxin gene-negative V. cholerae non-O1, non-O139 strain.
Cholera toxin (CT) gene-negative Vibrio cholerae non-O1, non-O139 strains may cause severe diarrhea though their pathogenic mechanism remains unclear. V. cholerae cytolysin (VCC) is a pore-forming exotoxin encoded in the hlyA gene of V. cholerae whose contribution to the pathogenesis is not fully understood. In this work, the virulence properties of a CT gene-negative V. cholerae non-O1, non-O139 strain causing a cholera-like syndrome were analyzed. Inoculation of rabbit ileal loops with the wild type strain induced extensive fluid accumulation, accompanied by severe histopathological damage characterized by villus shortening, lymphangiectasia and focal areas of necrosis. These pathogenic effects were abrogated by mutation of the hlyA gene thus pointing out the main role of VCC in the virulence of the strain. Interestingly, this toxin was capable of triggering apoptosis in human intestinal cell lines due to its anion channel activity. Moreover, the wild type strain also induced increased apoptosis of the intestinal epithelium cells which was not observed upon inoculation of the VCC null mutant strain, indicating that VCC may trigger apoptotic cell death during infection in vivo. Altogether, these results support a main role of VCC in the pathogenesis of the CT gene-negative V. cholerae non-O1, non-O139 strain and identify apoptosis as a previously unrecognized cell death pathway triggered by VCC.
Saka
Hector Alex
HA
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Centro de Investigaciones en Bioquímica e Inmunología ClBICI-CONICET, Córdoba, Argentina.
Bidinost
Carla
C
Sola
Claudia
C
Carranza
Pablo
P
Collino
Cesar
C
Ortiz
Susana
S
Echenique
Jose Ricardo
JR
Bocco
José Luis
JL
D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival; D002771:Cholera / Q000382:microbiology*; D002772:Cholera Toxin / Q000235:genetics; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000382:microbiology / Q000648:ultrastructure; D005122:Exudates and Transudates / Q000382:microbiology; D017353:Gene Deletion; D006460:Hemolysin Proteins / Q000235:genetics / Q000633:toxicity*; D006801:Humans; D007082:Ileum / Q000382:microbiology / Q000473:pathology; D008200:Lymphangiectasis / Q000382:microbiology; D046529:Microscopy, Electron, Transmission; D016254:Mutagenesis, Insertional; D009336:Necrosis / Q000382:microbiology; D011817:Rabbits; D044163:Vibrio cholerae non-O1 / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology
D001426:Bacterial Proteins; D006460:Hemolysin Proteins; D037521:Virulence Factors; C084287:hlyA protein, Vibrio cholerae; D002772:Cholera Toxin