Comparative Genome Analysis of Campylobacter fetus Subspecies Revealed Horizontally Acquired Genetic Elements Important for Virulence and Niche Specificity

Sabine Kienesberger,Ellen L Zechner,Gregor Gorkiewicz,Guillermo I Perez-Perez,Stella Wolfgruber,Martin J Blaser,Hanna Sprenger,Gerhard G Thallinger,Bettina Halwachs,Thomas Alter

doi:10.1371/journal.pone.0085491

Abstract

Campylobacter fetus are important animal and human pathogens and the two major subspecies differ strikingly in pathogenicity. C. fetus subsp. venerealis is highly niche-adapted, mainly infecting the genital tract of cattle. C. fetus subsp. fetus has a wider host-range, colonizing the genital- and intestinal-tract of animals and humans. We report the complete genomic sequence of C. fetus subsp. venerealis 84-112 and comparisons to the genome of C. fetus subsp. fetus 82-40. Functional analysis of genes predicted to be involved in C. fetus virulence was performed. The two subspecies are highly syntenic with 92% sequence identity but C. fetus subsp. venerealis has a larger genome and an extra-chromosomal element. Aside from apparent gene transfer agents and hypothetical proteins, the unique genes in both subspecies comprise two known functional groups: lipopolysaccharide production, and type IV secretion machineries. Analyses of lipopolysaccharide-biosynthesis genes in C. fetus isolates showed linkage to particular pathotypes, and mutational inactivation demonstrated their roles in regulating virulence and host range. The comparative analysis presented here broadens knowledge of the genomic basis of C. fetus pathogenesis and host specificity. It further highlights the importance of surface-exposed structures to C. fetus pathogenicity and demonstrates how evolutionary forces optimize the fitness and host-adaptation of these pathogens.

Highlights

The e-proteobacterial genus Campylobacter comprises bacteria with a high degree of niche adaptation and host tropism [1]
These features are typical for adaptation to a specific colonization niche and both species display strong host preference (‘‘tropism’’) [36,37]
Among Campylobacters, C. fetus subspecies are an exceptional model system to study the molecular basis of pathogen-host adaptation since, despite a highly clonal structure, they display strikingly dissimilar host preferences and tissue tropism

Summary

Introduction

The e-proteobacterial genus Campylobacter comprises bacteria with a high degree of niche adaptation and host tropism [1]. FGI II and VGI IV Contain CRISPR Loci We identified CRISPR-repeats on the genomes of both C. fetus subspecies (Figure S1). Venerealis 84-112 Displays Features Typical for Integrative Conjugative Elements (ICE) The extra-chromosomal element was designated as ICE_84-112 and is the first ICE described in C. fetus (physical map Figure S2; annotation details in File S3). Venerealis strains, 7 harbored the ICE-related genes (Table S6 in File S5).

Results

Conclusion