Small Antimicrobial Resistance Plasmids in Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC398

Abstract

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates of the clonal complex 398 are often resistant to a number of antimicrobial agents. Studies on the genetic basis of antimicrobial resistance in these bacteria identified SCCmec cassettes, various transposons and plasmids of different sizes that harbor antimicrobial resistance genes. While large plasmids that carry multiple antimicrobial resistance genes - occasionally together with heavy metal resistance genes and/or virulence genes - are frequently seen in LA-MRSA ST398, certain resistance genes are also associated with small plasmids of up to 15 kb in size. These small resistance plasmids usually carry only one, but in rare cases also two or three antimicrobial resistance genes. In the current review, we focus on small plasmids that carry the macrolide-lincosamide-streptogramin B resistance genes erm(C) or erm(T), the lincosamide resistance gene lnu(A), the pleuromutilin-lincosamide-streptogramin A resistance genes vga(A) or vga(C), the spectinomycin resistance gene spd, the apramycin resistance gene apmA, or the trimethoprim resistance gene dfrK. The detailed analysis of the structure of these plasmids allows comparisons with similar plasmids found in other staphylococci and underlines in many cases an exchange of such plasmids between LA-MRSA ST398 and other staphylococci including also coagulase-negative staphylococci.

Keywords: LA-MRSA; apmA; cfr; dfrK; erm; lnu(A); spd; vga.

FIGURE 1

Schematic presentation of the organization of (A) the two erm (C)-carrying plasmids pSWS371 and pSWS372, (B) the erm(T)-carrying plasmid pUR3912 and the chromosomal erm(T) region of MRSA ST398 isolate ST398NM01, (C) the lnu(A)-carrying plasmids pLNU1, pLNU9, pUR5425, and pBMSa1, and (D) the vga(A)- and the vga(C)-carrying plasmids pCPS32, pUR2355, pCPS49 and pKKS825 from MRSA ST398. The reading frames are presented as arrows with the arrowhead indicating the direction of transcription. A distance scale in kb is given below the maps. The resistance genes are indicated in red, plasmid replication genes rep in different shades of blue, and genes involved in plasmid recombination, mobilization and relaxation pre, mob, pre/mob, and rlx in different shades of yellow/-orange. The different blue and yellow-orange shadings indicate differences in the respective genes. In panel (A), the plasmid copy control gene cop-6 is displayed in gray and the staphylococcal recombination site A (RS_A) is indicated by a black box. In panel (B), the cadmium resistance operon cadDX is shown in pink and the IS431 elements and the IS712G element are displayed as black or gray boxes, respectively, with the white arrow inside representing the transposase gene tnp. The gray-shaded areas represent areas of at least > 95% sequence identity. This figure is modified from Lüthje et al. (2007) and Kadlec et al. (2010), Gómez-Sanz et al. (2013a), and Wendlandt et al. (2014b).

FIGURE 2

Schematic presentation of (A) the spd-carrying plasmids pDJ91S and pSWS2889 from MRSA ST398 in comparison to closely related plasmids pSWS2482 and pSWS1211 from S. hyicus, pSWS118 from S. chromogenes, and pSWS961 from S. equorum, (B) the apmA-carrying plasmid pKKS49 from MRSA ST398 and the dfrK-carrying plasmid pKKS966 from S. hyicus, and (C) the dfrK-carrying plasmid pKKS627 and the dfrK region of plasmid pKKS2187, both from MRSA ST398. The reading frames are presented as arrows with the arrowhead indicating the direction of transcription. A distance scale in kb is given below the maps. The resistance genes are indicated in red, plasmid replication genes rep in different shades of blue, and genes involved in plasmid recombination and mobilization, pre/mob and mob, in different shades of yellow/-orange. The different blue and yellow-orange shadings indicate differences in the respective genes. The IS257 elements in panel (C) are displayed as green boxes with the white arrow inside indicating the transposase gene tnp. The gray-shaded areas represent areas of at least > 99% sequence identity unless otherwise indicated. This figure is modified from Kadlec et al. (2012a) and Wendlandt et al. (2015b).