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Journal of Bacteriology, August 2009, p. 4750-4757, Vol. 191, No. 15
0021-9193/09/$08.00+0     doi:10.1128/JB.00189-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparative Genomics of the IncA/C Multidrug Resistance Plasmid Family{triangledown} ,{dagger}

W. Florian Fricke,1 Timothy J. Welch,2 Patrick F. McDermott,3 Mark K. Mammel,4 J. Eugene LeClerc,4 David G. White,3 Thomas A. Cebula,5 and Jacques Ravel1*

Institute for Genome Sciences (IGS), University of Maryland School of Medicine, Baltimore, Maryland 21201,1 National Center for Cool and Cold Water Aquaculture, United States Department of Agriculture, Kearneysville, West Virginia 25430,2 Center for Veterinary Medicine-Food and Drug Administration (CVM-FDA), Laurel, Maryland 20708,3 Center for Food Safety and Applied Nutrition-Food and Drug Administration (CFSAN-FDA), Laurel, Maryland 20708,4 Johns Hopkins University, Baltimore, Maryland 212185

Received 11 February 2009/ Accepted 14 May 2009

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.

* Corresponding author. Mailing address: Institute for Genome Sciences (IGS), University of Maryland School of Medicine, Baltimore, MD 21201. Phone: (301) 795-7884. Fax: (301) 838-0208. E-mail: jravel{at}som.umaryland.edu

{triangledown} Published ahead of print on 29 May 2009.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, August 2009, p. 4750-4757, Vol. 191, No. 15
0021-9193/09/$08.00+0     doi:10.1128/JB.00189-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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