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, timethoprim (Tp(r)), penicillin (Pc(r)) and the aminoglycosides gentamicin, tobramycin and kanamycin (Gm(r) Tm(r) Km(r)). Gm(r) Tm(r) Km(r) 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 Gm(r) Tm(r) Km(r) 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 Gm(r) Tm(r) Km(r) determinant homologous with that on Tn4001, occurs on conjugative plasmids from strains isolated in North America. Physical studies indicate that Pc(r), via a β-lactamase, and Tp(r), 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 (Em(r)), fusidic acid, methicillin (Mc(r)), minocycline, rifampicin, spectinomycin, streptomycin, sulphonamides, tetracycline (Tc(r)), cadmium (Cd(r)), and mercury (Hg(r)) are chromosomally encoded; these strains also possess chromosomally encoded Pc(r), via a β-lactamase. Evidence indicates that some of these determinants, Pc(r) , Cd(r), Hg(r) and Tc(r), 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. These studies, and reports from other laboratories which indicate that Em(r) and Mc(r) are encoded on the chromosome by site-specific transposons, support the hypothesis that multiresistance in the epidemic MRSA strains resulted predominantly from the accumulation of pre-evolved determinants. The possible origins of some determinants are described, as is evidence for the participation of other Gram-positive species, such as streptococci and coagulase-negative staphylococci, in the Staph. aureus gene pool.
|Number of pages||20|
|Journal||Journal of Antimicrobial Chemotherapy|
|Issue number||SUPPL. C|
|Publication status||Published - 1 Jan 1988|