Clinical impact of the type VI secretion system on virulence of Campylobacter species during infection

Abstract

Background The clinical course of Campylobacter infection varies in symptoms and severity depending on host factors, virulence of the pathogen and initiated therapy. The type VI secretion system (T6SS) has been identified as a novel virulence factor, which mediates contact-dependent injection of enzymes and toxins into competing bacteria or host cells and facilitates the colonisation of a host organism. We aimed to compare the clinical course of Campylobacter infection caused by strains with and without the T6SS and identify possible associations between this putative virulence factor and the clinical manifestations of disease. Methods From April 2015 to January 2017, patients with detection of Campylobacter spp. were identified at the University Hospital of Basel and the University Children’s Hospital of Basel and included in this case-control study. Presence of the T6SS gene cluster was assayed by PCR targeting the hcp gene, confirmed with whole genome sequencing. Pertinent clinical data was collected by medical record review. Differences in disease- and host-characteristics between T6SS-positive (case) and –negative (control) were compared in a uni- and multi-variable analysis. Hospital admission, antibiotic therapy, admission to intensive care unit, development of bacteraemia and in-hospital mortality were considered as clinical endpoints. Results We identified 138 cases of Campylobacter jejuni infections and 18 cases of Campylobacter coli infections from a paediatric and adult population. Analyses were focused on adult patients with C. jejuni ( n = 119) of which 16.8% were T6SS-positive. Comparisons between T6SS-positive and -negative C. jejuni isolates did not reveal significant differences regarding clinical manifestations or course of disease. All clinical endpoints showed a similar distribution in both groups. A higher score in the Charlson Comorbidity Index was associated with T6SS-positive C. jejuni isolates ( p < 0.001) and patients were more likely to have a solid organ transplant and to be under immunosuppressive therapy. Conclusions Our study does not provide evidence that T6SS is associated with a more severe clinical course. Interestingly, T6SS-positive isolates are more commonly found in immunocompromised patients: an observation which merits further investigation. Electronic supplementary material The online version of this article (10.1186/s12879-019-3858-x) contains supplementary material, which is available to authorized users.

Distribution of genes related to Type 6 secretion system and lipooligosaccharide that induced ganglioside mimicry among Campylobacter jejuni isolated from human diarrhea in Thailand

“…We found no significant association between hcp and C. jejuni isolates of any specific capsule type. This is similar to the finding by Agnetti et al [44], where no significant difference in the clinical manifestations and the course of disease between patient with hcppositive and -negative C. jejuni isolates. Similarly, the presence of hcp gene in C. jejuni and C. coli from stool did not have any significant association to clinical outcome in Egyptian children [43].…”

Genomic analysis of the diversity, antimicrobial resistance and virulence potential of clinical Campylobacter jejuni and Campylobacter coli strains from Chile

“…Campylobacter T6SS mutant strains exhibit colonization defects in both mouse [67] and chicken [69] in vivo infection models. The Campylobacter T6SS gene cluster is often encoded within the CjIE3 conjugative element in the chromosome of C. jejuni [61], but it can also be found in plasmids [70,71]. Our analysis identified the T6SS gene cluster in 9…”

“…This mutation is the most frequently reported mutation worldwide and confers high levels of resistance to fluoroquinolones [48,49]. To determine the virulence gene content of the C. jejuni and C. coli strains, we first assembled a list of 220 potential virulence genes, including genes described in the Virulence Factor Database [59] and genes reported to contribute to the virulence of Campylobacter in the literature [38,[60][61][62][63]. These genes were grouped into five distinct categories (adhesion and colonization, invasion, motility, secretion systems and toxins) and were used to screen each of the 81 genomes using BLASTn.…”

Genomic Analysis of Chilean Strains ofCampylobacter jejunifrom Human Faeces

“…However, in Campylobacter, the role in pathogenicity of T6SS is controversial. On the one hand, Agnetti et al [52] detected the T6SS in 16.8% cases of C. jejuni infections and observed no evidence of its association with a more severe clinical course, but these isolates were more commonly found in immunocompromised patients which merits further investigation. On the other hand, Lertpiriyapong et al [50] by means of in silico , in vitro , and in vivo analyses demonstrated that the T6SS in C. jejuni is functional and it exerts pleiotropic effects on two crucial processes: survival in a bile salt, deoxycholic acid (DCA), and host cell adherence and invasion.…”