Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour

Abstract

Heritable variation in behavioural traits generally has a complex genetic basis1, and thus naturally occurring polymorphisms that influence behaviour have been defined in only rare instances2,3. The isolation of wild strains of Caenorhabditis elegans has facilitated the study of natural genetic variation in this species4 and provided insights into its diverse microbial ecology5. C. elegans responds to bacterial infection with conserved innate immune responses6-8 and, while lacking the immunological memory of vertebrate adaptive immunity, exhibits an aversive learning response to pathogenic bacteria9. Here, we report the molecular characterization of naturally occurring coding polymorphisms in a C. elegans gene encoding a conserved HECT domain-containing E3 ubiquitin ligase, HECW-1. We show that two distinct polymorphisms in neighbouring residues of HECW-1 each affect C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa. Neuron-specific rescue and ablation experiments, and genetic interaction analysis suggest that HECW-1 functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through inhibition of the neuropeptide receptor NPR-110, which we have previously shown promotes P. aeruginosa lawn avoidance behaviour11. Our data establish a molecular basis for natural variation in a C. elegans behaviour that may undergo adaptive changes in response to microbial pathogens.

Behavioral avoidance of pathogenic bacteria by Caenorhabditis elegans

“…Then, after hours of exposure and presumed intestinal infection, C. elegans exhibits an altered preference for E. coli, suggestive of an aversive learning response [9] ( Figure 1A). In the absence of a choice between bacteria, when propagated monoaxenically on pathogens P. aeruginosa or Serratia marcescens, after an initial attractive phase, C. elegans exhibits a gradual evacuation of the bacterial lawn with kinetics comparable to the observed aversive learning response in the choice assay [10][11][12][13] ( Figure 1B). This lawn-leaving behavior likely reflects not only olfactory aversive learning but also the integration of multiple sensory cues from the bacterial lawn.…”

“…elegans can also use their mechanosensory neurons to respond to the texture of bacteria, slowing down once they have entered a bacterial lawn [6]. A naturally occurring polymorphism in the C. elegans E3 ubiquitin ligase HECW-1 affects lawn-leaving behavior by altering the mechanosensation of bacteria [13]. Reduction of function mutations in hecw-1 result in enhanced avoidance of P. aeruginosa.…”

“…Mutants lacking hecw-1 and OLLablated animals were observed to be defective in mechanosensation, implicating mechanosensory processes in the lawn-leaving behavior of P. aeruginosa. Finally, the enhanced avoidance and survival phenotypes of the hecw-1 mutant were suppressed by loss-of-function mutations in npr-1, suggesting that HECW-1 inhibits lawn-leaving by repressing activity of this neuropeptide receptor [13]. Thus, behaviors normally used to attract C. elegans to bacterial food sources, such as olfaction, aerotaxis, and mechanosensation, can be instrumental in promoting the avoidance behavior of pathogenic bacteria (Figure 2).…”

“…Polymorphisms between the Bristol N2 and Hawaiian strains of C. elegans have revealed evolutionarily derived differences in lawn-leaving behavior and survival on P. aeruginosa [12,13]. In the case of E3 ubiquitin ligase HECW-1, two naturally occurring polymorphisms were identified in several C. elegans wild isolates.…”

Pseudomonas fluorescens NZI7 repels grazing by C. elegans, a natural predator

“…Chang et al (2011) has demonstrated that pathogen avoidance by C. elegans can be affected by the lateral outer labial mechanosensory head neurons. tax mutants feeding on NZI7 grew well and showed no evidence of deleterious effects or pharyngeal dysfunction, allowing us to conclude that NZI7 is not intrinsically pathogenic to C. elegans and that the failure of wild-type nematodes to feed on it was due only to aversion and did not involve additional physical effects such as the pharyngeal blockage observed for C. elegans feeding on Y. pestis (Darby et al, 2002).…”