Probing the bacterial pathogenesis of ESKAPE species utilising C. elegans as a model system

Abstract

The nematode C. elegans is widely used as a model organism throughout biology, including as a host for bacterial infections. C. elegans can be exposed to a range of bacterial strains through presentation of bacteria as potential food sources in the form of a lawn on agar plates and can subsequently be observed. This thesis specifically examined strains from three Gram-negative species of the ESKAPE group, a group of troublesome antibiotic resistant and pathogenic bacterial pathogens. A range of strains from the Gram-negative ESKAPE species Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa were examined in C. elegans, and compared against E. coli OP50, the standard laboratory food source of the animal as a control. This allows similarities and differences between different bacterial strains to be identified as to how they affect C. elegans biology. C. elegans populations on lawns of OP50 show a progressive increase in leaving the bacterial lawn after extended exposure. This enhanced food-leaving was determined to be driven by C. elegans larvae that are produced by adult animals on the bacterial lawn. This was dependent on a homologue of the mammalian hormone oxytocin and indicates that this behaviour is related to signalling that controls parental behaviours in mammals. When C. elegans populations were examined on lawns of ESKAPE bacteria, some bacterial strains significantly reduced C. elegans lifespan, indicating pathogenicity, with different degrees of virulence being observed. In addition, individual pathogenic bacterial strains were found to generate a food aversion response in C. elegans, a previously reported indicator of bacterial pathogenicity. Further investigation revealed that neither colonisation nor the subsequent clearance of bacteria from the C. elegans intestine underpins the differential pathogenicity of these bacterial strains. Further analysis showed that neuropeptides are key modulators of the process of colonisation and act in both pathogenic and benign bacteria. Analysis of the food aversion provoked by pathogenic bacteria revealed that signalling by biogenic amines acts to modulate this behaviour. Specifically, serotonin acts to promote the food aversion response and octopamine acts to supress food aversion to specific pathogenic strains. From undertaking all these investigations, it can be seen that individual bacterial strains can exert diverse biological effects on C. elegans as a model host, and the comparative approach taken in this thesis allows insight to be made about individual and diverse bacterial strains. The result in this thesis provide further avenues for investigation as to how bacterial pathogenesis is mediated in C. elegans as a model host organism, specifically in terms of virulence factors present in different bacterial strains and further neural controls of the C. elegans biological response to bacteria.

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Identifiers

ORCID for Vincent O'connor: orcid.org/0000-0003-3185-5709

ORCID for Linda Holden-Dye: orcid.org/0000-0002-9704-1217

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