The Missing Pieces: The Role of Secretion Systems in Campylobacter jejuni Virulence

Abstract

Campylobacter jejuni is likely the most common bacterial cause of gastroenteritis worldwide, responsible for millions of cases of inflammatory diarrhea characterized by severe abdominal cramps and blood in the stool. Further, C. jejuni infections are associated with post-infection sequelae in developed countries and malnutrition and growth-stunting in low- and middle-income countries. Despite the increasing prevalence of the disease, campylobacteriosis, and the recognition that this pathogen is a serious health threat, our understanding of C. jejuni pathogenesis remains incomplete. In this review, we focus on the Campylobacter secretion systems proposed to contribute to host-cell interactions and survival in the host. Moreover, we have applied a genomics approach to defining the structural and mechanistic features of C. jejuni type III, IV, and VI secretion systems. Special attention is focused on the flagellar type III secretion system and the prediction of putative effectors, given that the proteins exported via this system are essential for host cell invasion and the inflammatory response. We conclude that C. jejuni does not possess a type IV secretion system and relies on the type III and type VI secretion systems to establish a niche and potentiate disease.

Genotypic Characterization and Antimicrobial Susceptibility of HumanCampylobacter jejuniIsolates in Southern Spain

“…This cluster has been detected in the chromosomal and plasmidic genomes of gram-positive bacteria such as Streptococcus (51). No antimicrobial resistance markers for erythromycin or type IV secretion (T4SS) were detected, which is consistent with the low prevalence of these genes in clinical isolates of C. jejuni (20, 42, 52).…”

Whole-genome sequencing reveals changes in genomic diversity and distinctive repertoires of T3SS and T6SS effector candidates in Chilean clinical Campylobacter strains

“…Therefore, the absence of these proteins may impact the virulence of these strains. Besides known fT3SS effector genes, we also detected important differences regarding the presence of 57 recently identified T3SS effector candidates (Gabbert et al, 2023). Based on the presence/absence of these putative effectors, the hierarchical analysis revealed five major subgroups with distinct effector repertoires (Figure 5).…”

“…Every Chilean isolate harbored previously described effectors, except for FspA1 and FspA2 that were absent in several isolates (Figure 5). The largest diversity was observed in terms of the presence of the effector candidates identified by Gabbert et al (Gabbert et al, 2023), especially in the motility/chemotaxis category. Predicted effectors related to glycan synthesis were absent in most Chilean isolates (Figure 5).…”

“…C. jejuni translocates at least ten effector proteins, contributing in vitro to host-cell adhesion and invasion and in vivo to colonization and immune modulation of infected chickens (Konkel et al, 1999;Barrero-Tobon and Hendrixson, 2012). Notably, a recent bioinformatic analysis predicted 57 putative fT3SS effector candidates encoded in the type strains F38011, NCTC 11168, and 81-176 (Gabbert et al, 2023), suggesting that the total number of effectors translocated by C. jejuni is more extensive than previously estimated. Some C. jejuni strains also encode for a T6SS (Robinson et al, 2021) which is a multiprotein contractile injection system that delivers effector proteins into target cells (Ho et al, 2014;Zoued et al, 2014;Coulthurst, 2019).…”

Flagellin O-linked glycans are required for the interactions between Campylobacter jejuni and Acanthamoebae castellanii

“…Immobile C. jejuni do not interact with A. castellanii C. jejuni requires its flagella for gut colonization, motility, secretion of virulence factors [16] and autoagglutination. Flagella promotes interactions with host cells, and biofilm and micro-colony formation [17].…”