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Hypoxia and the Hypoxic Response Pathway Protect against Pore-Forming Toxins in C. elegans

Summary: Hypoxia and the Hypoxic Response Pathway Protect
against Pore-Forming Toxins in C. elegans
Audrey Bellier1
, Chang-Shi Chen1
, Cheng-Yuan Kao1
, Hediye N. Cinar2
, Raffi V. Aroian1
1 Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California, United States of America, 2 United States Food and Drug
Administration, Center for Food Safety and Applied Nutrition, Division of Virulence Assessment, Laurel, Maryland, United States of America
Pore-forming toxins (PFTs) are by far the most abundant bacterial protein toxins and are important for the virulence of many
important pathogens. As such, cellular responses to PFTs critically modulate host-pathogen interactions. Although many
cellular responses to PFTs have been recorded, little is understood about their relevance to pathological or defensive
outcomes. To shed light on this important question, we have turned to the only genetic system for studying PFT-host
interactions--Caenorhabditis elegans intoxication by Crystal (Cry) protein PFTs. We mutagenized and screened for C. elegans
mutants resistant to a Cry PFT and recovered one mutant. Complementation, sequencing, transgenic rescue, and RNA
interference data demonstrate that this mutant eliminates a gene normally involved in repression of the hypoxia (low
oxygen response) pathway. We find that up-regulation of the C. elegans hypoxia pathway via the inactivation of three
different genes that normally repress the pathway results in animals resistant to Cry PFTs. Conversely, mutation in the


Source: Aroian, Raffi V. - Division of Biological Sciences, University of California at San Diego


Collections: Biology and Medicine