Multiresistant Staphylococcus aureus: genetics and evolution of epidemic Australian strains

Abstract

Molecular and genetic analysis of multiresistant isolates of Staphylococcus aureus from widely separated hospitals in Australia has demonstrated that these are clearly related, and that the predominant strains possess up to three different plasmids, which fall into the following classes: (i) small 1.6 kb plasmids, such as pSK3, which are phenotypically cryptic, (ii) 4.5 kb chloramphenicol resistance plasmids, such as pSK2, and (iii) the pSK1 family of multiresistance plasmids, which range in size from 20 to 42 kb and variously encode resistance to antiseptics and disinfectants, trimethoprim (Tpr), penicillin (Pcr) and the aminoglycosides gentamicin, tobramycin and kanamycin (Gmr Tmr Kmr). Gmr Tmr Kmr is encoded on the pSK1 family plasmids by transposon Tn4001, which was also detected on the chromosomes of some clinical isolates. Tn4001 is composed of inverted repeats of the insertion sequence IS256; these repeats flank a Gmr Tmr Kmr sequence encoding for a 57,000 dalton bifunctional protein with aminoglycoside acetyltransferase [AAC(6')] and phosphotransferase [APH(2")] activities. A Tn4001-like structure, which is defective in transposition but encodes for a Gmr Tmr Kmr determinant homologous with that on Tn4001, occurs on conjugative plasmids from strains isolated in North America. Physical studies indicate that Pcr, via a beta-lactamase, and Tpr, via a trimethoprim-insensitive dihydrofolate reductase (DHFR), are also encoded on the pSK1 family by transposons; these transposons have been designated Tn4002 and Tn4003, respectively. Tn4003 is flanked by direct repeats of the insertion sequence IS257. The evolution of the pSK1 family of multiresistance plasmids is traced through the transposition and genetic rearrangement of resistance determinants. Transposition and genetic rearrangement have also contributed to the evolution of a multiresistant chromosome in Staph. aureus. In the majority of contemporary multiply resistant Staph. aureus strains the determinants for resistance to erythromycin (Emr), fusidic acid, methicillin (Mcr), minocycline, rifampicin, spectinomycin, streptomycin, sulphonamides, tetracycline (Tcr), cadmium (Cdr), and mercury (Hgr) are chromosomally encoded; these strains also possess chromosomally encoded Pcr, via a beta-lactamase. Evidence indicates that some of these determinants, Pcr, Cdr, Hgr, and Tcr, were plasmid encoded in isolates collected from Australian hospitals prior to 1970. Through transposition and site-specific integration, they have since been acquired by the chromosome in more recent Staph. aureus strains.(ABSTRACT TRUNCATED AT 400 WORDS)

Potential Impact of Increased Use of Biocides in Consumer Products on Prevalence of Antibiotic Resistance

“…The multidrug efflux pumps qacA to qacG contribute to biocide tolerance in Staphylococcus aureus (230) and have been the subject of a number of excellent reviews (269)(270). These genes can become located on integrons and transferred between gram-positive organisms such as staphylococci and enterococci and also to gram-negative bacteria such as P. aeruginosa and the vibrios (135)(136).…”

Molecular Detection of Antimicrobial Resistance

“…The best-studied multidrug resistance elements are those which are often harbored by MRSA (316). Australian MRSA isolates may harbor up to three different plasmids: small (1.6-kb) cryptic plasmids, 4.5-kb chloramphenicol resistance plasmids, and 20-to 42-kb plasmids which variously encode resistance to antiseptics and disinfectants, trimethoprim, penicillin, gentamicin, tobramycin, and kanamycin.…”

Tn554 inserts in methicillin-resistant Staphylococcus aureus from Australia and England: comparison with an American methicillin-resistant group

“…aureus isolates contain chromosomal DNA, amounting to 30 kb or more, which is also absent from Mcs strains (Beck et al, 1986;Matsuhashi et al, 1986;Matthews et al, 1987). This DNA contains the Mc' determinant mec and determinants for various other resistances (Skinner el al., 1988;Skurray et al, 1988;Ubukata et al, 1989). It was proposed that Tn554 insert 6 of the New Jersey Mcr group might likewise be part of the rnec region (Tillotson et al, 1989).…”