Recruitment of LC3 by Campylobacter jejuni to Bacterial Invasion Site on Host Cells via the Rac1-Mediated Signaling Pathway.

Shiho Fukushima,Takaaki Shimohata,Kazuaki Mawatari,Akira Takahashi,Yuri Inoue,Takashi Uebanso,Junko Kido

doi:10.3389/fcimb.2022.829682

Shiho Fukushima, Takaaki Shimohata + Show 5 more

Open Access

https://doi.org/10.3389/fcimb.2022.829682

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Abstract

Campylobacter jejuni is a leading cause of food-borne disease worldwide. The pathogenicity of C. jejuni is closely associated with the internalization process in host epithelial cells, which is related to a host immune response. Autophagy indicates a key role in the innate immune system of the host to exclude invasive pathogens. Most bacteria are captured by autophagosomes and degraded by autophagosome-lysosome fusion in host cells. However, several pathogens, such as Salmonella and Shigella, avoid and/or escape autophagic degradation to establish infection. But autophagy involvement as a host immune response to C. jejuni infection has not been clarified. This study revealed autophagy association in C. jejuni infection. During infection, C. jejuni activated the Rho family small GTPase Rac1 signaling pathway, which modulates actin remodeling and promotes the internalization of this pathogen. In this study, we found the LC3 contribution to C. jejuni invasion signaling via the Rac1 signaling pathway. Interestingly, during C. jejuni invasion, LC3 was recruited to bacterial entry site depending on Rac1 GTPase activation just at the early step of the infection. C. jejuni infection induced LC3-II conversion, and autophagy induction facilitated C. jejuni internalization. Also, autophagy inhibition attenuated C. jejuni invasion step. Moreover, Rac1 recruited LC3 to the cellular membrane, activating the invasion of C. jejuni. Altogether, our findings provide insights into the new function of LC3 in bacterial invasion. We found the interaction between the Rho family small GTPase, Rac1, and autophagy-associated protein, LC3.

Highlights

Campylobacter jejuni is a Gram-negative spiral bacterium, which causes food-borne disease and induces gastroenteritis symptoms
We observed the localization of autophagy organelles and intracellular bacteria to estimate whether C. jejuni are targeted by xenophagy as with Salmonella and Shigella infection (Kageyama et al, 2011; Tattoli et al, 2012)
We investigated the correlation between the Rac1 signaling pathway above, and the other is the Rac1 activation pathway to alter the intracellular localization of LC3 and classical C. jejuni invasion-related Rac1 signaling

Summary

Introduction

Campylobacter jejuni is a Gram-negative spiral bacterium, which causes food-borne disease and induces gastroenteritis symptoms. Several studies have revealed the association of various factors in the pathogenicity of C. jejuni, such as motility, chemotaxis, and. Adhesion and invasion steps were considered the key factor of virulence in C. jejuni infection. Bacterial fibronectin-binding proteins, CadF and FlpA, are regarded as one of the main bacterial adherence factors that activate integrins and trigger host cytoskeletal rearrangement signaling pathway, and facilitate bacterial internalization (Konkel et al, 1997; Talukdar et al, 2020). Integrins a5b1 promote focal adhesion kinase (FAK) phosphorylation, which induces the activation of Rac GTPase and actin filament remodeling (Boehm et al, 2011; Eucker and Konkel, 2012). In C. jejuni infection, Rac GTPase activation enhanced the invasion of this pathogen (Boehm et al, 2011), so that it is regarded a crucial role in C. jejuni entry step into host epithelial cells

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