Intra Strain Variation of the Effects of Gram-Negative ESKAPE Pathogens on Intestinal Colonization, Host Viability, and Host Response in the Model Organism Caenorhabditis elegans

Abstract

In its native environment of rotting vegetation, the soil nematode Caenorhabditis elegans encounters a range of bacteria. This includes species from the ESKAPE group of pathogens that pose a clinical problem in acquired hospital infections. Here, we investigated three Gram-negative members of the ESKAPE group, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Pathogenicity profiles as measured by time to kill adult C. elegans showed that P. aeruginosa was the most pathogenic, followed by K. pneumoniae, while C. elegans cultured on A. baumannii exhibited the same survival as those on the standard laboratory food source for C. elegans, Escherichia coli OP50. The pathogenicity was paralleled by a reduction in time that C. elegans resided on the bacterial lawn with the most pathogenic strains triggering an increase in the frequency of food-leaving. Previous reports indicate that gut colonization is a feature of pathogenicity, but we found that the most pathogenic strains were not associated with the highest level of colonization. Indeed, clearance of P. aeruginosa strains from the C. elegans gut was independent of bacterial pathogenicity. We show that this clearance is regulated by neuromodulation as C. elegans mutants in unc-31 and egl-3 have enhanced clearance of P. aeruginosa. Intriguingly this is also not linked to their pathogenicity. It is likely that there is a dynamic balance occurring in the C. elegans intestinal environment between maintaining a healthy, beneficial microbiota and removal of pathogenic bacteria.