Abstract
Campylobacter jejuni is a leading cause of food-borne illness. Although a natural reservoir of the pathogen is domestic poultry, the degree of genomic diversity exhibited by the species limits the application of epidemiological methods to trace specific infection sources. Bacteriophage predation is a common burden placed upon C. jejuni populations in the avian gut, and we show that amongst C. jejuni that survive bacteriophage predation in broiler chickens are bacteriophage-resistant types that display clear evidence of genomic rearrangements. These rearrangements were identified as intra-genomic inversions between Mu-like prophage DNA sequences to invert genomic segments up to 590 kb in size, the equivalent of one-third of the genome. The resulting strains exhibit three clear phenotypes: resistance to infection by virulent bacteriophage, inefficient colonisation of the broiler chicken intestine, and the production of infectious bacteriophage CampMu. These genotypes were recovered from chickens in the presence of virulent bacteriophage but not in vitro. Reintroduction of these strains into chickens in the absence of bacteriophage results in further genomic rearrangements at the same locations, leading to reversion to bacteriophage sensitivity and colonisation proficiency. These findings indicate a previously unsuspected method by which C. jejuni can generate genomic diversity associated with selective phenotypes. Genomic instability of C. jejuni in the avian gut has been adopted as a mechanism to temporarily survive bacteriophage predation and subsequent competition for resources, and would suggest that C. jejuni exists in vivo as families of related meta-genomes generated to survive local environmental pressures.
Highlights
The Gram-negative bacterium Campylobacter jejuni is recognised as a major cause of human gastroenteritis worldwide [1] and has been linked to serious neurological sequelae such as Guillain–Barresyndrome and Miller–Fisher syndrome [2]
As part of a study to investigate bacteriophage therapy and its impact on Campylobacter populations in poultry, we report that chromosomal inversions of up to 590 kb that include the origin of replication of C. jejuni arise in response to exposure to virulent bacteriophage
Predation of C. jejuni by virulent bacteriophage offers the prospect of controlling bacterial populations at source in poultry
Summary
The Gram-negative bacterium Campylobacter jejuni is recognised as a major cause of human gastroenteritis worldwide [1] and has been linked to serious neurological sequelae such as Guillain–Barresyndrome and Miller–Fisher syndrome [2]. Poultry are considered a major source of C. jejuni infections in humans, though numerous other risk factors have been proposed, including the consumption of pork, barbequing, living or working on farms, working in slaughterhouses, seasonal changes in flying insect populations, travel abroad, and the consumption of raw milk [3,4,5,6,7,8]. C. jejuni exhibits slipstrand mutation within homopolymeric tracts, which is thought to alter the expression of a significant number of genes [11]. The majority of these genes have been identified as being involved in the production of surface structures, including key fitness determinants such as motility [12,13,14] and lipo-oligosaccharide synthesis [15]. C. jejuni is known to be naturally competent under environmental conditions [16,17], though analyses of multi-locus sequence typing (MLST) profiles indicate that short lengths of DNA
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