Multi-Omics of Campylobacter jejuni Growth in Chicken Exudate Reveals Molecular Remodelling Associated with Altered Virulence and Survival Phenotypes

鸡渗出液中空肠弯曲菌生长的多组学研究揭示了与毒力和存活表型改变相关的分子重塑

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Abstract

Campylobacter jejuni is the leading cause of foodborne human gastroenteritis in the developed world. Infections are largely acquired from poultry produced for human consumption and poor food handling is thus a major risk factor. Chicken exudate (CE) is a liquid produced from defrosted commercial chicken products that facilitates C. jejuni growth. We examined the response of C. jejuni to growth in CE using a multi-omics approach. Changes in the C. jejuni proteome were assessed by label-based liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We quantified 1328 and 1304 proteins, respectively, in experiments comparing 5% CE in Mueller-Hinton (MH) medium and 100% CE with MH-only controls. These proteins represent 81.8% and 80.3% of the predicted C. jejuni NCTC11168 proteome. Growth in CE induced profound remodelling of the proteome. These changes were typically conserved between 5% and 100% CE, with a greater magnitude of change observed in 100% CE. We confirmed that CE induced C. jejuni biofilm formation, as well as increasing motility and resistance against oxidative stress, consistent with changes to proteins representing those functions. Assessment of the C. jejuni metabolome showed CE also led to increased intracellular abundances of serine, proline, and lactate that were correlated with the elevated abundances of their respective transporters. Analysis of carbon source uptake showed prolonged culture supernatant retention of proline and succinate in CE-supplemented medium. Metabolomics data provided preliminary evidence for the uptake of chicken-meat-associated dipeptides. C. jejuni exposed to CE showed increased resistance to several antibiotics, including polymyxin B, consistent with changes to tripartite efflux system proteins and those involved in the synthesis of lipid A. The C. jejuni CE proteome was also characterised by very large increases in proteins associated with iron acquisition, while a decrease in proteins containing iron-sulphur clusters was also observed. Our data suggest CE is both oxygen- and iron-limiting and provide evidence of factors required for phenotypic remodelling to enable C. jejuni survival on poultry products.

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