Abstract
We studied conjugative plasmids encoding high-level mupirocin resistance. These plasmids were found in Staphylococcus aureus isolates from two geographic locations in the United States. Transfer genes on three mupirocin resistance plasmids with different restriction endonuclease profiles were indistinguishable by DNA hybridization from those on pG01, a conjugative aminoglycoside resistance plasmid representative of similar plasmids that are prevalent in the United States. One mupirocin resistance plasmid, pG0400 (34 kb), was smaller than pG01 (52 kb) because of the absence from pG0400 of DNA, found on pG01, that contained genes encoding resistance to aminoglycosides, trimethoprim, and quaternary ammonium compounds flanked by directly repeated copies of the insertion sequence (IS)-like element IS431-IS257. The plasmids pG0400 and pG01 were otherwise indistinguishable except for the presence in pG0400 of a 4.5-kb HinDIII fragment encoding mupirocin resistance. The added mupirocin resistance gene was flanked by two directly repeated copies of IS431/257. The nucleotide sequence of DNA contiguous to the outside of the IS elements, as well as those of the elements themselves, was identical in both pG01 and pG0400, and there were no target site duplications flanking either copy of the element. We conclude that the mupirocin resistance gene was added to an existing conjugative plasmid in conjunction with the deletion of other resistance genes by recombination at IS elements. The construction of conjugative plasmids carrying a mupirocin resistance gene may be a model for the mobility of other resistance genes newly acquired by staphylococci.
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- Archer G. L., Johnston J. L. Self-transmissible plasmids in staphylococci that encode resistance to aminoglycosides. Antimicrob Agents Chemother. 1983 Jul;24(1):70–77. doi: 10.1128/aac.24.1.70. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Archer G. L., Scott J. Conjugative transfer genes in staphylococcal isolates from the United States. Antimicrob Agents Chemother. 1991 Dec;35(12):2500–2504. doi: 10.1128/aac.35.12.2500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barberis-Maino L., Berger-Bächi B., Weber H., Beck W. D., Kayser F. H. IS431, a staphylococcal insertion sequence-like element related to IS26 from Proteus vulgaris. Gene. 1987;59(1):107–113. doi: 10.1016/0378-1119(87)90271-x. [DOI] [PubMed] [Google Scholar]
- Bolivar F., Rodriguez R. L., Greene P. J., Betlach M. C., Heyneker H. L., Boyer H. W., Crosa J. H., Falkow S. Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. Gene. 1977;2(2):95–113. [PubMed] [Google Scholar]
- Boyer H. W., Roulland-Dussoix D. A complementation analysis of the restriction and modification of DNA in Escherichia coli. J Mol Biol. 1969 May 14;41(3):459–472. doi: 10.1016/0022-2836(69)90288-5. [DOI] [PubMed] [Google Scholar]
- Byrne M. E., Gillespie M. T., Skurray R. A. 4',4'' adenyltransferase activity on conjugative plasmids isolated from Staphylococcus aureus is encoded on an integrated copy of pUB110. Plasmid. 1991 Jan;25(1):70–75. doi: 10.1016/0147-619x(91)90008-k. [DOI] [PubMed] [Google Scholar]
- Byrne M. E., Gillespie M. T., Skurray R. A. Molecular analysis of a gentamicin resistance transposonlike element on plasmids isolated from North American Staphylococcus aureus strains. Antimicrob Agents Chemother. 1990 Nov;34(11):2106–2113. doi: 10.1128/aac.34.11.2106. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Casewell M. W., Hill R. L. Mupirocin ('pseudomonic acid')--a promising new topical antimicrobial agent. J Antimicrob Chemother. 1987 Jan;19(1):1–5. doi: 10.1093/jac/19.1.1. [DOI] [PubMed] [Google Scholar]
- Cederna J. E., Terpenning M. S., Ensberg M., Bradley S. F., Kauffman C. A. Staphylococcus aureus nasal colonization in a nursing home: eradication with mupirocin. Infect Control Hosp Epidemiol. 1990 Jan;11(1):13–16. doi: 10.1086/646072. [DOI] [PubMed] [Google Scholar]
- Cookson B. D. Mupirocin resistance in staphylococci. J Antimicrob Chemother. 1990 Apr;25(4):497–501. doi: 10.1093/jac/25.4.497. [DOI] [PubMed] [Google Scholar]
- Dyke K. G., Curnock S. P., Golding M., Noble W. C. Cloning of the gene conferring resistance to mupirocin in Staphylococcus aureus. FEMS Microbiol Lett. 1991 Jan 15;61(2-3):195–198. doi: 10.1016/0378-1097(91)90550-t. [DOI] [PubMed] [Google Scholar]
- Firth N., Ridgway K. P., Byrne M. E., Fink P. D., Johnson L., Paulsen I. T., Skurray R. A. Analysis of a transfer region from the staphylococcal conjugative plasmid pSK41. Gene. 1993 Dec 22;136(1-2):13–25. doi: 10.1016/0378-1119(93)90442-6. [DOI] [PubMed] [Google Scholar]
- Fuller A. T., Mellows G., Woolford M., Banks G. T., Barrow K. D., Chain E. B. Pseudomonic acid: an antibiotic produced by Pseudomonas fluorescens. Nature. 1971 Dec 17;234(5329):416–417. doi: 10.1038/234416a0. [DOI] [PubMed] [Google Scholar]
- Galetto D. W., Johnston J. L., Archer G. L. Molecular epidemiology of trimethoprim resistance among coagulase-negative staphylococci. Antimicrob Agents Chemother. 1987 Nov;31(11):1683–1688. doi: 10.1128/aac.31.11.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilbart J., Perry C. R., Slocombe B. High-level mupirocin resistance in Staphylococcus aureus: evidence for two distinct isoleucyl-tRNA synthetases. Antimicrob Agents Chemother. 1993 Jan;37(1):32–38. doi: 10.1128/aac.37.1.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goering R. V., Ruff E. A. Comparative analysis of conjugative plasmids mediating gentamicin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1983 Sep;24(3):450–452. doi: 10.1128/aac.24.3.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill R. L., Duckworth G. J., Casewell M. W. Elimination of nasal carriage of methicillin-resistant Staphylococcus aureus with mupirocin during a hospital outbreak. J Antimicrob Chemother. 1988 Sep;22(3):377–384. doi: 10.1093/jac/22.3.377. [DOI] [PubMed] [Google Scholar]
- Hodgson J. E., Curnock S. P., Dyke K. G., Morris R., Sylvester D. R., Gross M. S. Molecular characterization of the gene encoding high-level mupirocin resistance in Staphylococcus aureus J2870. Antimicrob Agents Chemother. 1994 May;38(5):1205–1208. doi: 10.1128/aac.38.5.1205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hughes J., Mellows G. Inhibition of isoleucyl-transfer ribonucleic acid synthetase in Escherichia coli by pseudomonic acid. Biochem J. 1978 Oct 15;176(1):305–318. doi: 10.1042/bj1760305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janssen D. A., Zarins L. T., Schaberg D. R., Bradley S. F., Terpenning M. S., Kauffman C. A. Detection and characterization of mupirocin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1993 Sep;37(9):2003–2006. doi: 10.1128/aac.37.9.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kauffman C. A., Terpenning M. S., He X., Zarins L. T., Ramsey M. A., Jorgensen K. A., Sottile W. S., Bradley S. F. Attempts to eradicate methicillin-resistant Staphylococcus aureus from a long-term-care facility with the use of mupirocin ointment. Am J Med. 1993 Apr;94(4):371–378. doi: 10.1016/0002-9343(93)90147-h. [DOI] [PubMed] [Google Scholar]
- Kreiswirth B. N., Löfdahl S., Betley M. J., O'Reilly M., Schlievert P. M., Bergdoll M. S., Novick R. P. The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature. 1983 Oct 20;305(5936):709–712. doi: 10.1038/305709a0. [DOI] [PubMed] [Google Scholar]
- Layton M. C., Patterson J. E. Mupirocin resistance among consecutive isolates of oxacillin-resistant and borderline oxacillin-resistant Staphylococcus aureus at a university hospital. Antimicrob Agents Chemother. 1994 Jul;38(7):1664–1667. doi: 10.1128/aac.38.7.1664. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Layton M. C., Perez M., Heald P., Patterson J. E. An outbreak of mupirocin-resistant Staphylococcus aureus on a dermatology ward associated with an environmental reservoir. Infect Control Hosp Epidemiol. 1993 Jul;14(7):369–375. doi: 10.1086/646764. [DOI] [PubMed] [Google Scholar]
- McDonnell R. W., Sweeney H. M., Cohen S. Conjugational transfer of gentamicin resistance plasmids intra- and interspecifically in Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother. 1983 Jan;23(1):151–160. doi: 10.1128/aac.23.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morton T. M., Eaton D. M., Johnston J. L., Archer G. L. DNA sequence and units of transcription of the conjugative transfer gene complex (trs) of Staphylococcus aureus plasmid pGO1. J Bacteriol. 1993 Jul;175(14):4436–4447. doi: 10.1128/jb.175.14.4436-4447.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moy J. A., Caldwell-Brown D., Lin A. N., Pappa K. A., Carter D. M. Mupirocin-resistant Staphylococcus aureus after long-term treatment of patients with epidermolysis bullosa. J Am Acad Dermatol. 1990 May;22(5 Pt 1):893–895. doi: 10.1016/0190-9622(90)70120-7. [DOI] [PubMed] [Google Scholar]
- Rahman M., Connolly S., Noble W. C., Cookson B., Phillips I. Diversity of staphylococci exhibiting high-level resistance to mupirocin. J Med Microbiol. 1990 Oct;33(2):97–100. doi: 10.1099/00222615-33-2-97. [DOI] [PubMed] [Google Scholar]
- Rahman M., Noble W. C., Cookson B. Transmissible mupirocin resistance in Staphylococcus aureus. Epidemiol Infect. 1989 Apr;102(2):261–270. doi: 10.1017/s0950268800029939. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ranelli D. M., Jones C. L., Johns M. B., Mussey G. J., Khan S. A. Molecular cloning of staphylococcal enterotoxin B gene in Escherichia coli and Staphylococcus aureus. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5850–5854. doi: 10.1073/pnas.82.17.5850. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reagan D. R., Doebbeling B. N., Pfaller M. A., Sheetz C. T., Houston A. K., Hollis R. J., Wenzel R. P. Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment. Ann Intern Med. 1991 Jan 15;114(2):101–106. doi: 10.7326/0003-4819-114-2-101. [DOI] [PubMed] [Google Scholar]
- Rouch D. A., Messerotti L. J., Loo L. S., Jackson C. A., Skurray R. A. Trimethoprim resistance transposon Tn4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS257. Mol Microbiol. 1989 Feb;3(2):161–175. doi: 10.1111/j.1365-2958.1989.tb01805.x. [DOI] [PubMed] [Google Scholar]
- Schaberg D. R., Power G., Betzold J., Forbes B. A. Conjugative R plasmids in antimicrobial resistance of Staphylococcus aureus causing nosocomial infections. J Infect Dis. 1985 Jul;152(1):43–49. doi: 10.1093/infdis/152.1.43. [DOI] [PubMed] [Google Scholar]
- Scully B. E., Briones F., Gu J. W., Neu H. C. Mupirocin treatment of nasal staphylococcal colonization. Arch Intern Med. 1992 Feb;152(2):353–356. [PubMed] [Google Scholar]
- Stewart P. R., Dubin D. T., Chikramane S. G., Inglis B., Matthews P. R., Poston S. M. IS257 and small plasmid insertions in the mec region of the chromosome of Staphylococcus aureus. Plasmid. 1994 Jan;31(1):12–20. doi: 10.1006/plas.1994.1002. [DOI] [PubMed] [Google Scholar]
- Sutherland R., Boon R. J., Griffin K. E., Masters P. J., Slocombe B., White A. R. Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicrob Agents Chemother. 1985 Apr;27(4):495–498. doi: 10.1128/aac.27.4.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas W. D., Jr, Archer G. L. Identification and cloning of the conjugative transfer region of Staphylococcus aureus plasmid pGO1. J Bacteriol. 1989 Feb;171(2):684–691. doi: 10.1128/jb.171.2.684-691.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas W. D., Jr, Archer G. L. Mobility of gentamicin resistance genes from staphylococci isolated in the United States: identification of Tn4031, a gentamicin resistance transposon from Staphylococcus epidermidis. Antimicrob Agents Chemother. 1989 Aug;33(8):1335–1341. doi: 10.1128/aac.33.8.1335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winter R. B., Gold L. Overproduction of bacteriophage Q beta maturation (A2) protein leads to cell lysis. Cell. 1983 Jul;33(3):877–885. doi: 10.1016/0092-8674(83)90030-2. [DOI] [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]