A Genomic Island Defines Subspecies-Specific Virulence Features of the Host-Adapted Pathogen Campylobacter fetus subsp. venerealis

Abstract

The pathogen Campylobacter fetus comprises two subspecies, C. fetus subsp. fetus and C. fetus subsp. venerealis. Although these taxa are highly related on the genome level, they are adapted to distinct hosts and tissues. C. fetus subsp. fetus infects a diversity of hosts, including humans, and colonizes the gastrointestinal tract. In contrast, C. fetus subsp. venerealis is largely restricted to the bovine genital tract, causing epidemic abortion in these animals. In light of their close genetic relatedness, the specific niche preferences make the C. fetus subspecies an ideal model system to investigate the molecular basis of host adaptation. In this study, a subtractive-hybridization approach was applied to the genomes of the subspecies to identify different genes potentially underlying this specificity. The comparison revealed a genomic island uniquely present in C. fetus subsp. venerealis that harbors several genes indicative of horizontal transfer and that encodes the core components necessary for bacterial type IV secretion. Macromolecular transporters of this type deliver effector molecules to host cells, thereby contributing to virulence in various pathogens. Mutational inactivation of the putative secretion system confirmed its involvement in the pathogenicity of C. fetus subsp. venerealis.

Interbacterial Macromolecular Transfer by the Campylobacter fetus subsp. venerealis Type IV Secretion System

“…venerealis, we additionally created a gene disruption in virD4 of a particularly virulent field isolate C. fetus subsp. venerealis 84-112 (28). Comparison of the DNA mobilization capacity of this mutant and the parent strain verified the importance of virD4 in gene transfer (Table 5).…”

“…The mutant vir derivatives of C. fetus subsp. venerealis ATCC 19438 strains were shown in our earlier work to attenuate virulence during infection of cultured human cells (28). Plasmid transfer efficiencies were compared when the wild-type parental strains and mutants C. fetus subsp.…”

“…Mutational inactivation of the virD4 and virB9 components in virulent C. fetus subsp. venerealis isolates attenuated invasion and cell-killing phenotypes in cultured human cell lines (28). Nonetheless, progress in understanding the role this chromosomally encoded T4SS plays in host-pathogen interactions remains challenging; this is due to the difficulty of manipulating the organism genetically and also to the current absence of wellcharacterized in vitro models of tissue-specific infection (34).…”

“…Several virulenceassociated T4SS appear to have retained the capacity to mobilize plasmids by conjugation, while gaining proficiency in specific protein translocation (10,69). Our work with the human and animal pathogen Campylobacter fetus recently revealed a subspecies-specific pathogenicity island (PAI) encoding a functional bacterial T4a secretion apparatus (28). This pathogen belongs to the group of epsilonproteobacteria and is highly adapted to mucosal surfaces (31).…”

Inconsistency of Phenotypic and Genomic Characteristics of Campylobacter fetus Subspecies Requires Reevaluation of Current Diagnostics

“…Two genomic islands (GIs) that encoded a type IV secretion system (T4SS), as defined by Kienesberger et al (9,13), were identified in the chromosomes of the closed C. fetus genomes. These two chromosomally located T4SS regions were present in strains that were distributed over the two core genome clusters (Table 1).…”