From pathogen to a commensal: modification of the Microbacterium nematophilum-Caenorhabditis elegans interaction during chronic infection by the absence of host insulin signalling.

Maria Gravato-Nobre,Petros Ligoxygakis,Jonathan Hodgkin

doi:10.1242/bio.053504

Abstract

ABSTRACTThe nematode worm Caenorhabditis elegans depends on microbes in decaying vegetation as its food source. To survive in an environment rich in opportunistic pathogens, C. elegans has evolved an epithelial defence system where surface-exposed tissues such as epidermis, pharynx, intestine, vulva and hindgut have the capacity of eliciting appropriate immune defences to acute gut infection. However, it is unclear how the worm responds to chronic intestinal infections. To this end, we have surveyed C. elegans mutants that are involved in inflammation, immunity and longevity to find their phenotypes during chronic infection. Worms that grew in a monoculture of the natural pathogen Microbacterium nematophilum (CBX102 strain) had a reduced lifespan and vigour. This was independent of intestinal colonisation as both CBX102 and the derived avirulent strain UV336 were early persistent colonisers. In contrast, the long-lived daf-2 mutant was resistant to chronic infection, showing reduced colonisation and higher vigour. In fact, UV336 interaction with daf-2 resulted in a host lifespan extension beyond OP50, the Escherichia coli strain used for laboratory C. elegans culture. Longevity and vigour of daf-2 mutants growing on CBX102 was dependent on the FOXO orthologue DAF-16. Our results indicate that the interaction between host genotype and strain-specific bacteria determines longevity and health for C. elegans.

Highlights

Animal epithelia from hydra to humans possess innate mechanisms that sense pathogenic and toxic insults and transmit non-self/danger recognition signals to activate appropriate defences (Zasloff 2002; Bartlett 2008; Augustin et al, 2012)
chronic gastrointestinal infections (CGIs) reduced host lifespan (Fig. 1A) and health measured by vigour of movement in liquid assays (Fig. 1B)
Bacteria associated with the animal gut are important for gastrointestinal function (Fischbach 2018)

Summary

Introduction

Animal epithelia from hydra to humans possess innate mechanisms that sense pathogenic and toxic insults and transmit non-self/danger recognition signals to activate appropriate defences (Zasloff 2002; Bartlett 2008; Augustin et al, 2012). The efficacy of these systems determines whether microbial populations can be controlled, and organismal homeostasis maintained. Elegans is a bacterial feeder that spends much of its life in decomposing vegetable matter and depends on microbes as its food source (Frezal and Felix 2015) These microbes are ground by the pharynx before they subsequently enter the gut. To survive in an environment rich in potentially damaging microorganisms, C. elegans has evolved an epithelial defence system coupled with the ability to discriminate between pathogenic vs. edible bacteria (reviewed in Kim and Ewbank, 2018).

Methods

Results

Conclusion