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TITLE:  Comparative genomics of the IncA/C multidrug resistance plasmid family
AUTHORS:  Fricke WF;Welch TJ;McDermott PF;Mammel MK;Leclerc JE;White DG;Cebula TA;Ravel J;
YEAR:  2009
JOURNAL FULL:  Journal of bacteriology
VOLUME:  191
ISSUE:  15
END PAGE:  4757
KEYWORDS:  Aeromonas;Aeromonas hydrophila;Algorithms;analysis;Drug Resistance,Multiple,Bacterial;Escherichia coli;genetics;Genomics;Maryland;Models,Genetic;Molecular Sequence Data;Phylogeny;physiology;Plasmids;Research;Salmonella;Sequence Analysis,DNA;
ABSTRACT:  Multidrug resistance (MDR) plasmids belonging to the IncA/C plasmid family are widely distributed among Salmonella and other enterobacterial isolates from agricultural sources and have, at least once, also been identified in a drug-resistant Yersinia pestis isolate (IP275) from Madagascar. Here, we present the complete plasmid sequences of the IncA/C reference plasmid pRA1 (143,963 bp), isolated in 1971 from the fish pathogen Aeromonas hydrophila, and of the cryptic IncA/C plasmid pRAx (49,763 bp), isolated from Escherichia coli transconjugant D7-3, which was obtained through pRA1 transfer in 1980. Using comparative sequence analysis of pRA1 and pRAx with recent members of the IncA/C plasmid family, we show that both plasmids provide novel insights into the evolution of the IncA/C MDR plasmid family and the minimal machinery necessary for stable IncA/C plasmid maintenance. Our results indicate that recent members of the IncA/C plasmid family evolved from a common ancestor, similar in composition to pRA1, through stepwise integration of horizontally acquired resistance gene arrays into a conserved plasmid backbone. Phylogenetic comparisons predict type IV secretion-like conjugative transfer operons encoded on the shared plasmid backbones to be closely related to a group of integrating conjugative elements, which use conjugative transfer for horizontal propagation but stably integrate into the host chromosome during vegetative growth. A hipAB toxin-antitoxin gene cluster found on pRA1, which in Escherichia coli is involved in the formation of persister cell subpopulations, suggests persistence as an early broad-spectrum antimicrobial resistance mechanism in the evolution of IncA/C resistance plasmids
AFFILIATIONS:  Institute for Genome Sciences (IGS), University of Maryland School of Medicine, Baltimore, MD 21201, USA