Abstract

Campylobacter jejuni is a Gram-negative foodborne pathogen that causes diarrheal disease and is associated with severe post-infectious sequelae. Bacteriophages (phages) are a possible means of reducing Campylobacter colonization in poultry to prevent downstream human infections. However, the factors influencing phage-host interactions must be better understood before this strategy can be predictably employed. Most studies have focused on Campylobacter phage binding to the host surface, with all phages classified as either capsule- or flagella-specific. Here we describe the characterization of a C. jejuni phage that requires functional flagellar glycosylation and motor genes for infection, without needing the flagella for adsorption to the cell surface. Through phage infectivity studies of targeted C. jejuni mutants, transcriptomic analysis of phage-resistant mutants, and genotypic and phenotypic analysis of a spontaneous phage variant capable of simultaneously overcoming flagellar gene dependence and sensitivity to oxidative stress, we have uncovered a link between oxidative stress, flagellar motility, and phage infectivity. Taken together, our results underscore the importance of understanding phage-host interactions beyond the cell surface and point to host oxidative stress state as an important and underappreciated consideration for future phage-host interaction studies.

Highlights

  • Campylobacter jejuni is an important Gram-negative foodborne pathogen worldwide that causes diarrheal disease and is associated with severe post-infectious sequelae, such as Guillain-Barré syndrome, irritable bowel syndrome, growth stunting and arthritis [1,2,3].reports of antibiotic resistance continue to increase, and alternative solutions are required to combat this pathogen [4,5]

  • Our results point to a complex interplay between phage infectivity, oxidative stress and the flagellar motility pathway in C. jejuni, underscoring the importance of understanding phage-host interactions beyond the cell surface

  • To determine whether flagellar glycosylation is important for National Collection of Type Cultures (NCTC) 12673 infection, we examined phage infection of ∆pseC, ∆pseF, ∆pseG, ∆pseH mutants and found that we examined phage infection of ΔpseC, ΔpseF, ΔpseG, ΔpseH mutants and found that comcompared to wild type C. jejuni NCTC 11168 infection (EOP set to 100%), infectivity was pared to wild type C. jejuni NCTC 11168 infection (EOP set to 100%), infectivity was dedecreased on all mutants (Figure 1)

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Summary

Introduction

Campylobacter jejuni is an important Gram-negative foodborne pathogen worldwide that causes diarrheal disease and is associated with severe post-infectious sequelae, such as Guillain-Barré syndrome, irritable bowel syndrome, growth stunting and arthritis [1,2,3]. Reports of antibiotic resistance continue to increase, and alternative solutions are required to combat this pathogen [4,5]. Bacteriophages (phages), the viruses that infect bacteria, are highly abundant in all environments harbouring bacteria. Because of their natural ability to recognize and kill their hosts, along with their ability to evolve and adapt alongside their hosts, the exploitation of phages has been considered as a possible antimicrobial strategy [7]. Phage-host interaction studies have provided valuable insights into bacterial evolution [8]

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