Burkholderia pseudomallei kills Caenorhabditis elegans through virulence mechanisms distinct from intestinal lumen colonization.
The nematode Caenorhabditis elegans is hypersusceptible to Burkholderia pseudomallei infection. However, the virulence mechanisms underlying rapid lethality of C. elegans upon B. pseudomallei infection remain poorly defined. To probe the host-pathogen interaction, we constructed GFP-tagged B. pseudomallei and followed bacterial accumulation within the C. elegans intestinal lumen. Contrary to slow-killing by most bacterial pathogens, B. pseudomallei caused fairly limited intestinal lumen colonization throughout the period of observation. Using grinder-defective mutant worms that allow the entry of intact bacteria also did not result in full intestinal lumen colonization. In addition, we observed a significant decline in C. elegans defecation and pharyngeal pumping rates upon B. pseudomallei infection. The decline in defecation rates ruled out the contribution of defecation to the limited B. pseudomallei colonization. We also demonstrated that the limited intestinal lumen colonization was not attributed to slowed host feeding as bacterial loads did not change significantly when feeding was stimulated by exogenous serotonin. Both these observations confirm that B. pseudomallei is a poor colonizer of the C. elegans intestine. To explore the possibility of toxin-mediated killing, we examined the transcription of the C. elegans ABC transporter gene, pgp-5, upon B. pseudomallei infection of the ppgp-5::gfp reporter strain. Expression of pgp-5 was highly induced, notably in the pharynx and intestine, compared with Escherichia coli-fed worms, suggesting that the host actively thwarted the pathogenic assaults during infection. Collectively, our findings propose that B. pseudomallei specifically and continuously secretes toxins to overcome C. elegans immune responses.
School of Biosciences and Biotechnology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.
Soon-Keat
SK
Ooi
Tian-Yeh
TY
Lim
Song-Hua
SH
Lee
Sheila
S
Nathan
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology / Q000378:metabolism*; D019121:Burkholderia Infections / Q000276:immunology* / Q000473:pathology; D016957:Burkholderia pseudomallei / Q000472:pathogenicity*; D017173:Caenorhabditis elegans / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity; D049452:Green Fluorescent Proteins / Q000235:genetics; D054884:Host-Pathogen Interactions; D007422:Intestines / Q000382:microbiology; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D014774:Virulence
D018528:ATP-Binding Cassette Transporters; D001427:Bacterial Toxins; D029742:Caenorhabditis elegans Proteins; C581813:PGP-5 protein, C elegans; D015800:Protozoan Proteins; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins