Acanthamoeba castellaniias a model for unveilingCampylobacter jejunihost-pathogen dynamics

Abstract

AbstractThe persistence of the major enteric pathogenCampylobacter jejuniin the natural environment, despite being microaerophilic, remains unsolved. Its survival in the natural atmospheric environment likely stems from several factors, including interactions with amoebae.C. jejunitransiently interacts with Acanthamoebae and this is thought to provide protection against unfavourable atmospheric conditions and subsequently prime the bacteria for interactions with warm-blooded hosts. Acanthamoebae play vital roles in microbial ecosystems by preying on bacterial species, some of which are clinically important. We analysed the whole transcriptome ofA. castellaniiinfected withC. jejuni11168H. Our findings provide evidence that infection ofA. castellaniiwithC. jejunitriggers distinct and reproducible cellular responses. Upregulated genes were associated with protein synthesis, DNA damage and repair, gluconeogenic pathways, and protein folding and targeting, while downregulated genes were involved in calcium ion transport, osmotic stress response, energy reserve metabolic processes, and protein hydroxylation. From this data we characterized Cj0979c, named hereC. jejuniendonuclease (CjeN), which induces DNA damage inA. castellanii. High-resolution microscopy revealed an unexpected association betweenC. jejuniand host mitochondria, while infected cells show elevated cytosolic calcium levels and metabolic changes favouring “Warburg-like” metabolism. The increased lactate production was subsequently depleted, suggesting that this host metabolic by-product may supportC. jejunisurvival. These findings identify an unexpected interaction between amoebae and a microaerophilic bacterium and provides a useful model for further research on host-pathogen interactions.