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Science 323 (5912): 382-384

Copyright © 2009 by the American Association for the Advancement of Science

A Polymorphism in npr-1 Is a Behavioral Determinant of Pathogen Susceptibility in C. elegans

Kirthi C. Reddy,1* Erik C. Andersen,2,3* Leonid Kruglyak,2,3{dagger} Dennis H. Kim1{dagger}

Abstract: The nematode Caenorhabditis elegans responds to pathogenic bacteria with conserved innate immune responses and pathogen avoidance behaviors. We investigated natural variation in C. elegans resistance to pathogen infection. With the use of quantitative genetic analysis, we determined that the pathogen susceptibility difference between the laboratory wild-type strain N2 and the wild isolate CB4856 is caused by a polymorphism in the npr-1 gene, which encodes a homolog of the mammalian neuropeptide Y receptor. We show that the mechanism of NPR-1–mediated pathogen resistance is through oxygen-dependent behavioral avoidance rather than direct regulation of innate immunity. For C. elegans, bacteria represent food but also a potential source of infection. Our data underscore the importance of behavioral responses to oxygen levels in finding an optimal balance between these potentially conflicting cues.

1 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Howard Hughes Medical Institute, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
3 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: leonid{at}genomics.princeton.edu (L.K.); dhkim{at}mit.edu (D.H.K.)

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