Campylobacter jejuni Virulence Factors Identified by Modulating Their Synthesis on Ribosomes With Altered rRNA Methylation.

Agnieszka Sałamaszyńska-Guz,Stephen Douthwaite,Pernille Kronholm Rasmussen,Małgorzata Murawska

doi:10.3389/fcimb.2021.803730

Agnieszka Sałamaszyńska-Guz, Stephen Douthwaite + Show 2 more

Open Access

https://doi.org/10.3389/fcimb.2021.803730

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Abstract

Campylobacter jejuni is a major cause of food poisoning worldwide, and remains the main infective agent in gastroenteritis and related intestinal disorders in Europe and the USA. As with all bacterial infections, the stages of adhesion to host tissue, survival in the host and eliciting disease all require the synthesis of proteinaceous virulence factors on the ribosomes of the pathogen. Here, we describe how C. jejuni virulence is attenuated by altering the methylation of its ribosomes to disrupt the composition of its proteome, and how this in turn provides a means of identifying factors that are essential for infection and pathogenesis. Specifically, inactivation of the C. jejuni Cj0588/TlyA methyltransferase prevents methylation of nucleotide C1920 in the 23S rRNA of its ribosomes and reduces the pathogen’s ability to form biofilms, to attach, invade and survive in host cells, and to provoke the innate immune response. Mass spectrometric analyses of C. jejuni TlyA-minus strains revealed an array of subtle changes in the proteome composition. These included reduced amounts of the cytolethal distending toxin (CdtC) and the MlaEFD proteins connected with outer membrane vesicle (OMV) production. Inactivation of the cdtC and mlaEFD genes confirmed the importance of their encoded proteins in establishing infection. Collectively, the data identify a subset of genes required for the onset of human campylobacteriosis, and serve as a proof of principle for use of this approach in detecting proteins involved in bacterial pathogenesis.

Highlights

Campylobacter jejuni infections are the leading cause of human bacterial gastroenteritis in developed countries, and are characterized by attachment and invasion of the colonic epithelium leading to inflammation of the bowel and diarrheal disease
We reported that loss of TlyA methylation at nucleotide C1920 in 23S rRNA attenuates several virulence traits of C. jejuni
Loss of some rRNA modifications have been reported to cause a series of pleiotropic effects, presumably due to changes in protein expression, and can result in reduced virulence in pathogenic bacteria (Sergiev et al, 2018)

Summary

Introduction

Campylobacter jejuni infections are the leading cause of human bacterial gastroenteritis in developed countries, and are characterized by attachment and invasion of the colonic epithelium leading to inflammation of the bowel and diarrheal disease. Identification of Campylobacter jejuni Virulence Factors colitis (Johnson et al, 2017) Provoking this range of pathogenic effects undoubtedly requires the coordinated expression of a series of C. jejuni genes that are dedicated to virulence. This pathogen must first survive the handling and cleaning processes such as those involved in the slaughter of chickens and the preparation of meat products (Hermans et al, 2011; Rasschaert et al, 2020); after consumption, the pathogen must remain viable in the human gut to initiate the steps of colonization; and subsequently, when established, the visible symptoms of gastrointestinal disease ensue upon production of virulence factors including toxins (Kreling et al, 2020; Elmi et al, 2021).

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