Genomic analysis of immune response against Vibrio cholerae hemolysin in Caenorhabditis elegans.
Vibrio cholerae cytolysin (VCC) is among the accessory V. cholerae virulence factors that may contribute to disease pathogenesis in humans. VCC, encoded by hlyA gene, belongs to the most common class of bacterial toxins, known as pore-forming toxins (PFTs). V. cholerae infects and kills Caenorhabditis elegans via cholerae toxin independent manner. VCC is required for the lethality, growth retardation and intestinal cell vacuolation during the infection. However, little is known about the host gene expression responses against VCC. To address this question we performed a microarray study in C. elegans exposed to V. cholerae strains with intact and deleted hlyA genes.Many of the VCC regulated genes identified, including C-type lectins, Prion-like (glutamine [Q]/asparagine [N]-rich)-domain containing genes, genes regulated by insulin/IGF-1-mediated signaling (IIS) pathway, were previously reported as mediators of innate immune response against other bacteria in C. elegans. Protective function of the subset of the genes up-regulated by VCC was confirmed using RNAi. By means of a machine learning algorithm called FastMEDUSA, we identified several putative VCC induced immune regulatory transcriptional factors and transcription factor binding motifs. Our results suggest that VCC is a major virulence factor, which induces a wide variety of immune response- related genes during V. cholerae infection in C. elegans.
Division of Virulence Assessment, Food and Drug Administration, Laurel, Maryland, United States of America.
Surasri N
SN
Sahu
Jada
J
Lewis
Isha
I
Patel
Serdar
S
Bozdag
Jeong H
JH
Lee
Joseph E
JE
LeClerc
Hediye Nese
HN
Cinar
D020816:Amino Acid Motifs; D000818:Animals; D001413:Bacillus thuringiensis / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics / Q000379:methods; D006460:Hemolysin Proteins / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000276:immunology; D034622:RNA Interference; D013696:Temperature; D014158:Transcription, Genetic; D056811:Unfolded Protein Response / Q000235:genetics; D014734:Vibrio cholerae / Q000276:immunology* / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D029742:Caenorhabditis elegans Proteins; D006460:Hemolysin Proteins; D037521:Virulence Factors; C073845:hemolysin, Vibrio