Genome Dynamics of Campylobacter jejuni in Response to Bacteriophage Predation

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.

Bacteriophage F336 Recognizes the Capsular Phosphoramidate Modification of Campylobacter jejuni NCTC11168

“…One of these, named 11168R, was further characterized. Previously, loss of motility and genomic rearrangements have been associated with phage resistance development in C. jejuni (8,46). Phenotypic characterization showed that neither the motility nor the ability to autoagglutinate had changed in 11168R ( Table 2), indicating that the flagella and components important for cell-to-cell interactions were unaffected by the bacteriophage F336 resistance phenotype.…”

“…For Campylobacter, only little is known about how phages recognize this bacterium, and to date no phage receptors have been identified. However, previous studies imply that both the capsule and the flagella of Campylobacter could be involved in the recognition by phages (8,46). Thus, the initial phage-host interaction is highly understudied for this bacterium.…”

“…However, despite many reports, phage resistance development has been investigated in only two studies. In one study, resistance was a result of genomic rearrangements between Mu-like prophage elements of the investigated C. jejuni strain (46). Another study found that changes in the capsule and loss of motility resulted in phage resistance in Campylobacter, but the actual mechanisms behind this remains to be elucidated (8).…”

Movers and shakers

“…118 This phenomenon was observed for phage resistant derivatives of Campylobacter jejuni which were unable to efficiently colonize the broiler chicken intestine. 119 Recent studies have demonstrated that phage resistant mutants may have functional properties that differ from those of the parental strain. Phage resistant derivatives of Lactobacillus delbreuckii strains demonstrated either a preserved or enhanced ability to activate the small intestinal immune response of BALB/C mice who received pure preparations of phage sensitive or phage resistant cultures over 7 consecutive days.…”

Phages as Therapeutic Tools to Control Major Foodborne Pathogens: Campylobacter and Salmonella

“…Nevertheless some of the above mentioned studies found that phage resistance can be associated with a reduced colonization potential in the chicken intestine, suggesting that there is a fitness cost to phage resistance in which phage-resistant Campylobacter revert to a sensitive phenotype when re-colonizing the chicken intestine in the absence of phage predation. It was also suggested that genomic instability of C. jejuni in the avian gut can be seen as a mechanism to temporarily survive phage predation and later competition for resources (Carvalho et al, 2010a;Loc Carrillo et al, 2005;Scott et al, 2007a;Scott et al, 2007b). Conversely, recent studies by reported that Campylobacter strains resistant to phage infection were recovered from phage-treated chickens at a frequency of 13% and that these resistant phenotypes did not exhibit a reduced ability to colonize the chicken guts and did not revert to sensitive types (Carvalho et al, 2010a).…”