Abstract
BackgroundThe spread of bacterial plasmids is an increasing global problem contributing to the widespread dissemination of antibiotic resistance genes including β-lactamases. Our understanding of the details of the biological mechanisms by which these natural plasmids are able to persist in bacterial populations and are able to establish themselves in new hosts via conjugative transfer is very poor. We recently identified and sequenced a globally successful plasmid, pCT, conferring β-lactam resistance.ResultsHere, we investigated six plasmid encoded factors (tra and pil loci; rci shufflon recombinase, a putative sigma factor, a putative parB partitioning gene and a pndACB toxin-antitoxin system) hypothesised to contribute to the ‘evolutionary success’ of plasmid pCT. Using a functional genomics approach, the role of these loci was investigated by systematically inactivating each region and examining the impact on plasmid persistence, conjugation and bacterial host biology. While the tra locus was found to be essential for all pCT conjugative transfer, the second conjugation (pil) locus was found to increase conjugation frequencies in liquid media to particular bacterial host recipients (determined in part by the rci shufflon recombinase). Inactivation of the pCT pndACB system and parB did not reduce the stability of this plasmid.ConclusionsOur findings suggest the success of pCT may be due to a combination of factors including plasmid stability within a range of bacterial hosts, a lack of a fitness burden and efficient transfer rates to new bacterial hosts rather than the presence of a particular gene or phenotype transferred to the host. The methodology used in our study could be applied to other ‘successful’ globally distributed plasmids to discover the role of currently unknown plasmid backbone genes or to investigate other factors which allow these elements to persist and spread.
Highlights
The spread of bacterial plasmids is an increasing global problem contributing to the widespread dissemination of antibiotic resistance genes including β-lactamases
Using a functional genomic approach analogous to that which has been broadly employed in studying chromosomal genes of various eukaryotic and prokaryotic organisms, we examined the impact of plasmid genes on pCT persistence and conjugation and upon the bacterial host
Furuya and Komano (1996) showed that when the pndACB operon, similar to that found on the IncI plasmid R64 was inactivated, R64 was rapidly lost from the bacterial population, it was required for maintenance of R64 over a similar time period [24]
Summary
The spread of bacterial plasmids is an increasing global problem contributing to the widespread dissemination of antibiotic resistance genes including β-lactamases. Bacterial plasmids are widely recognised for their role in the expansion and dissemination of virulence and antibiotic resistance genes both between members of the same species and to new bacterial hosts of different species [1,2] Their ability to acquire and spread either single or multiple antibiotic resistance genes to pathogens has become a considerable problem and an obstacle to successful therapeutic treatment [3]. The recent emergence of genes including β-lactamases which confer resistance to the commonly used β-lactam class of antibiotics, can largely be attributed to the spread and persistence of successful plasmids in a wide range of bacterial hosts [5,6,7] Despite their importance and the recently generated wealth of plasmid sequence data [8], our knowledge of the factors which allow plasmids to maintain antibiotic resistance genes, to remain stable in bacterial populations in the absence of selective pressure, and to successfully spread to different bacterial strains is very poor
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
