CapC, a Novel Autotransporter and Virulence Factor of Campylobacter jejuni

Abstract

is recognized as an important causative agent of bacterial gastroenteritis in the developed world. Despite the identification of several factors contributing to infection, characterization of the virulence strategies employed by remains a significant challenge. Bacterial autotransporter proteins are a major class of secretory proteins in Gram-negative bacteria, and notably, many autotransporter proteins contribute to bacterial virulence. The aim of this study was to characterize the 81116 C8J_1278 gene (), predicted to encode an autotransporter protein, and examine the contribution of this factor to virulence of The predicted CapC protein has a number of features that are consistent with autotransporters, including the N-terminal signal sequence and the C-terminal β-barrel domain and was determined to localize to the outer membrane. Inactivation of the gene in 81116 and M1 resulted in reduced insecticidal activity in larvae. Furthermore, mutants displayed significantly reduced adherence to and invasion of nonpolarized, partially differentiated Caco-2 and T84 intestinal epithelial cells. Gentamicin treatment showed that the reduced invasion of the mutant is primarily caused by reduced adherence to intestinal epithelial cells, not by reduced invasion capability. mutants caused reduced interleukin 8 (IL-8) secretion from intestinal epithelial cells and elicited a significantly diminished immune reaction in larvae, indicating that CapC functions as an immunogen. In conclusion, CapC is a new virulence determinant of that contributes to the integral infection process of adhesion to human intestinal epithelial cells. is a major causative agent of human gastroenteritis, making this zoonotic pathogen of significant importance to human and veterinary public health worldwide. The mechanisms by which interacts with intestinal epithelial cells and causes disease are still poorly understood due, in part, to the heterogeneity of infection biology. Given the importance of to public health, the need to characterize novel and existing virulence mechanisms is apparent. The significance of our research is in demonstrating the role of CapC, a novel virulence factor in that contributes to adhesion and invasion of the intestinal epithelium, thereby in part, addressing the dearth of knowledge concerning the factors involved in pathogenesis and the variation observed in the severity of human infection.

Eleutherine americana extract inhibits adherence to and invasion of Caco‐2 cells by commonly contaminated Campylobacter spp. in food

“…Adhesion is a preliminary step required for the initial attachment of the pathogenic bacteria to the host cell surface. The successive adhesion process leads to the further invasion of the attached bacteria into the host tissue resulting in the secretion of the pathogenic factors within the host cells (Krachler & Orth, ; Mehat, Part, Van Vliet, & La Ragione, ). Thus, the aforementioned steps play critical role in the pathogenesis of the bacteria.…”

“…An important step in campylobacter pathogenesis is adherence to intestinal mucosa (Mehat et al, ; Zhu, Hua, Hou, & Zhao, ). Adherence of campylobacters to host cells is associated with protein factors (Young, Davis, & Dirita, ).…”

“…Adherence of campylobacters to host cells is associated with protein factors (Young, Davis, & Dirita, ). Several proteins contribute to adherence of Campylobacter to eukaryotic cells (Castillo, Heredia, Contreras, & Garcia, ; Mehat et al, ). Earlier reports suggest that polyphenolic constituents from plants such as alkaloids, flavonoids, quinones, naphthoquinones, and anthraquinones possess anti‐adhesive property against campylobacter (Bensch et al, ; Castillo et al, ; Gomez Castellanos, Prieto, & Heinrich, ).…”

Campylobacter jejuni and Campylobacter coli autotransporter genes exhibit lineage-associated distribution and decay

“…These autotransporter genes exhibited considerable sequence divergence in the N-terminal "passenger" domain yet share significant identity in their C-terminal domains ( Fig. 1a) [25,28]. The phylogenetic tree in Fig.…”

“…These surface-exposed or secreted proteins share a mechanism of export, conferred by their C-terminal β-barrel structure whilst virulence properties are conferred by their N-terminal functional or "passenger" domain [24]. We recently described the CapC autotransporter in the commonly utilised reference strains C. jejuni 81,116 [26] and C. jejuni M1 [27], which is absent in the reference isolates C. jejuni NCTC 11168 and C. jejuni 81-176 [28]. Advances in sequencing technology have resulted in the public availability of large collections of genome sequences of C. jejuni and C. coli [29], which have been used to show distinct distribution patterns of gene families involved in pathogenesis, metabolism and stress responses [23,[30][31][32].…”