Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences.

Xing Zhang,Benjamin W Harding,Jonathan J Ewbank,Nathalie Pujol,Jia-Xuan Chen,Damien Courtine,Dina Aggad,Danielle A Garsin

doi:10.1371/journal.pgen.1009600

Abstract

Animals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second increases STA-2 levels in the nucleus, modifies the nucleolus, and, potentially as a consequence of a host surveillance mechanism, causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens.

Highlights

The co-evolution of host and pathogen species can be interpreted as a constant arms race, with rounds of reciprocal adaptations driving diversification and divergence on the molecular and macroscopic scales [1]
We study a simple animal host, the nematode worm C. elegans and its natural enemy, the fungus Drechmeria coniospora, which has a large repertoire of uncharacterised potential “virulence factors”
By producing each enterotoxin inside the epidermis of C. elegans, we were able to study their specific effect on the host, and in particular on the way in which they altered the host’s immune defences

Summary

Introduction

The co-evolution of host and pathogen species can be interpreted as a constant arms race, with rounds of reciprocal adaptations driving diversification and divergence on the molecular and macroscopic scales [1]. The endogenous fungal gene could be engineered so that the resultant protein is tagged to allow its visualisation during infection and/or for the use of biochemistry to identify host protein targets. Both these strategies have been applied to D. coniospora [2]. In order to study candidate virulence factors, we adopted a strategy to express the corresponding genes directly in C. elegans. We showed that expressing the Shigella virulence factor OspF (a MAP kinase inhibitor) in the epidermis of C. elegans blocked the induction of the antimicrobial (AMP) gene nlp-29 [5], one of the hallmarks of the innate immune response to D. coniospora infection [6]. Given the toxic nature of some virulence factors, we refined the method to allow tight control of transgene expression, in the adult epidermis of C. elegans

Methods

Results

Discussion

Conclusion