Gentamicin Resistance Plasmids Research Articles

Increasing incidence of resistance to gentamicin and related aminoglycosides in Salmonella typhimurium phage type 204c in England, Wales and Scotland.

Phage type 204c of Salmonella typhimurium (DT 204c) appeared in bovine animals in 1979. It is now the predominant type in cattle in England, Wales and Scotland and ranks in the 10 most common phage types in humans. All strains of DT 204c have been resistant to at least four antimicrobial drugs. In 1979 and 1980 the most common resistance pattern was that of chloramphenicol, streptomycin, sulphonamides, tetracyclines and trimethoprim (CSSuTTm) but since 1981 strains with additional resistance to ampicillin and neomycin-kanamycin (AK) have predominated. Strains resistant to furazolidone (Fu) have caused sporadic outbreaks. Gentamicin resistance (G) appeared in DT 204c in 1983 and gentamicin-resistant strains are increasing in incidence. With the exception of resistance to furazolidone, drug resistance in DT 204c has been plasmid-mediated. Characterisation of gentamicin resistance plasmids in DT 204c of R-type ACGKSSuTTm has demonstrated the existence of three distinct lines, two of which have been found exclusively in cattle and one in cattle and humans. The misguided and often inappropriate use of antimicrobial drugs in calves has contributed to the appearance of multiresistant strains of DT 204c and positive measures to limit range and levels of antimicrobials available to feed manufacturers may be necessary.

Interspecific co-transfer of antibiotic resistance plasmids in staphylococci in vivo.

The co-transfer of plasmid-borne genes governing resistance to gentamicin, tetracycline, erythromycin and chloramphenicol has been demonstrated on human and mouse skin. Two different gentamicin resistance plasmids have been studied in detail; both appear to have the ability to mobilize in vivo otherwise non-transferable resistance plasmids from coagulase-negative to coagulase-positive staphylococci. This emphasis the role of the skin in maintaining a pool of resistance genes available to pathogenic staphylococci.

Transposition of gentamicin resistance to staphylococcal plasmids encoding resistance to cationic agents.

Plasmid pWG115 isolated from a methicillin-resistant Staphylococcus aureus encodes resistance to cationic surface-active agents and trimethoprim. It has a molecular weight of ca 14.6 megadaltons and can be transferred to other strains of staphylococci in mixed-culture transfer with propamidine isethionate as a selective agent. Gentamicin resistance in Australian methicillin-resistant Staph. aureus isolates can be either chromosomal or plasmid-borne. The most common gentamicin resistance plasmid is 18.0 megadaltons and also encodes resistance to trimethoprim and cationic surface-active agents. This suggested that pWG115 was related to gentamicin resistance plasmids and that it may provide a target for the postulated gentamicin resistance transposon. This paper demonstrates that the chromosomal gentamicin resistance determinant from WG523 can transpose into pWG115 to generate an 18.0 megadalton plasmid, phenotypically indistinguishable from the naturally occurring gentamicin resistance plasmids such as pWG53. EcoR1 restriction enzyme analysis demonstrated that gentamicin resistance can transpose into at least two sites on pWG115. One of these sites generates EcoR1 restriction fragments identical to pWG53. The 5.2 kilobase pair (3.4 megadalton) element involved confers low-level resistance to gentamicin, cross resistance to tobramycin and kanamycin, and has been designated Tn3851.

Analysis of plasmids mediating gentamicin resistance in methicillin-resistant Staphylococcus aureus.

Gentamicin-resistance plasmids in methicillin-resistant Staphylococcus aureus isolated from four Australian hospitals have been studied. All the plasmids conferred resistance to gentamicin, tobramycin, kanamycin and all but one conferred resistance to quarternary ammonium compounds. Plasmids which only carried these resistance determinants were ca 15.3 megadaltons and were only found in isolates from one hospital. The most common plasmid was ca 18.0 megadaltons and in addition encoded trimethoprim resistance. Two plasmids, one of ca 19.6 megadaltons and one of ca 28.5 megadaltons were found to carry the penicillinase determinant. However only the larger of these encoded heavy metal ion resistance and was sensitive to quaternary ammonium compounds. EcoR1 analysis indicated that all but the ca 28.5 megadalton plasmid were closely related. The EcoR1 analysis of the ca 28.5 megadalton plasmid indicated that it could have resulted from recombination between a gentamicin resistance determinant and a penicillinase plasmid.

Genetics of drug resistance in methicillin-resistant Staphylococcus aureus from Australian hospitals

The drug-resistance determinants in methicillin-resistant Staphylococcus aureus (MRSA) from three different hospitals in Eastern Australia have been examined. With one exception, all the isolates had chromosomal determinants for penicillinase and resistance to cadmium (Cd), mercury (Hg), phenyl mercuric acetate, methicillin, tetracycline, erythromycin, lincomycin and low level streptomycin. The strain which was the exception differed in that it did not have chromosomal resistance to Cd and lincomycin. In addition, the strains often contained plasmids which belonged to one of three categories: a small cryptic plasmid of either c. 1·4 Mdal, c. 1·7 Mdal or c. 1·9 Mdal; a chloramphenicol resistance plasmid of c. 2·8 Mdal; and a gentamicin resistance plasmid within the range of c. 15·3 to c. 28·5 Mdal. The predominant gentamicin-resistant plasmid in isolates from two hospitals had a molecular weight of c. 18 Mdal, whereas the isolates from the third hospital had a plasmid of molecular weight c. 15·3 Mdal. The only other gentamicin resistance plasmids detected were associated with penicillinase determinants. In one isolate, this corresponded to a plasmid of c. 19·6 Mdal and in the other to a plasmid of c. 28·5 Mdal. These results indicate that MRSAs which are prevalent in Eastern Australian hospitals are substantially different in the location of their drug resistance determinants to earlier strains reported in the literature.

Conjugational transfer of gentamicin resistance plasmids intra- and interspecifically in Staphylococcus aureus and Staphylococcus epidermidis

We have previously reported the transfer of gentamicin resistance (Gmr) plasmids in a mixed culture inter- and intraspecifically between strains of Staphylococcus aureus and Staphylococcus epidermidis isolated at Michael Reese Hospital (Jaffe et al., Antimicrob. Agents Chemother. 21:773-779, 1982). We have now shown that representatives of these plasmids were transferred between apparently nonlysogenic strains of S. aureus either in mixed culture in broth or by filter-mating on agar medium. The mechanism of transfer appeared to be conjugation. A transferable Gmr plasmid (pSH8) mobilized or cotransferred a tetracycline R-plasmid and a chloramphenicol R-plasmid that were not independently transferable. The transfer of Gmr plasmids was accompanied by a high incidence of deletion mutations with varied loss of plasmid resistance determinants and, with some mutants, loss of the ability to effect self-transfer. Restriction endonuclease digestion of pSH8 and its deletion mutants made it possible to assign the property of self-transfer to a specific segment of the pSH8 genome and provided the basis for a physical and genetic map of that plasmid. Similar Gmr plasmids from S. aureus strains isolated in locations remote from Michael Reese Hospital had resistance determinants and transfer properties comparable to those of pSH8. Our observations provide evidence for the conjugal transfer of some staphylococcal plasmids, apparently independent of the presence of phage. This mechanism may be of significance in the intra- and interspecific dissemination of resistance to aminoglycosides and other antibiotics in Staphylococcus spp.

Structural and phenotypic varieties of gentamicin resistance plasmids in hospital strains of Staphylococcus aureus and coagulase-negative staphylococci

We previously described a neonatal nursery epidemic of infections caused by a single strain of Staphylococcus aureus bearing a gentamicin resistance plasmid (Vogel et al., Antimicrob. Agents Chemother. 13:466-472, 1978). The same plasmid was present in two isolates of Staphylococcus epidermidis from the patients in this nursery and was transferable interspecifically from either S. aureus or S. epidermidis. During the ensuing 3 years, in the absence of further epidemics, we collected 162 gentamicin-resistant strains of S. aureus and coagulase-negative staphylococci from patients distributed throughout our hospital. Gentamicin resistance plasmids obtained from 41 representative S. aureus and coagulase-negative staphylococcal strains differed as determined by phenotypic and molecular analyses from the plasmid in the neonatal nursery epidemic. Nevertheless, these plasmids were structurally related to each other and to the plasmid of the original epidemic. Our results suggest an evolutionary relationship among these plasmids and support the hypothesis of a genetic reservoir of gentamicin resistance in coagulase-negative staphylococci transferable to S. aureus.

Distribution of transferable trimethoprim and gentamicin resistance plasmids in Enterobacteriaceae

Following the employment of trimethoprim/sulfonamid and gentamicin in the general clinical praxis transferable plasmids with respective resistance function were identified at first in enteric bacteria from sewage before they could be detected in patient strains. Whereas the trimethoprim resistance plasmids represent different incompatibility groups (C, FII, I5, K, M, N, S, U) the gentamicin resistance plasmids are very similar IncM members of 62 MD in size. Therefore a clonal distribution of a particular gentamicin resistance plasmid has to be taken into consideration.

Verbreitung transferabler Trimethoprimresistenz‐ und Gentamicinresistenzplasmide in Enterobacteriaceae

AbstractFollowing the employment of trimethoprim/sulfonamid and gentamicin in the general clinical praxis transferable plasmids with respective resistance functions were identified at first in enteric bacteria from sewage before they could be detected in patient strains. Whereas the trimethoprim resistance plasmids represent different incompatibility groups (C, FII, I5, K, M, N, S, U) the gentamicin resistance plasmids are very similar IncM members of 62 MD in size. Therefore a clonal distribution of a particular gentamicin resistance plasmid has to be taken into consideration.

Identity and interspecific transfer of gentamicin-resistance plasmids in Staphylococcus aureus and Staphylococcus epidermidis.

The hypothesis that emergence of gentamicin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis in a neonatal special care nursery was the result of transfer of a single plasmid between these two species was examined. In experiments with mixtures of staphylococci, either in mixed cultures or on human skin, isolates of S. aureus and S. epidermidis transferred their gentamicin-resistance plasmids both intra- and interspecifically. By electron microscopy, the molecular masses of the plasmids from S. aureus and S. epidermidis were the same, 12.2 +/- 0.36 (standard deviation) and 12.3 +/- 0.56 megadaltons, respectively. Restriction endonuclease analysis of the plasmids from five isolates of S. aureus and two isolates of S. epidermidis, with use of the enzymes HaeIII, EcoRI, XbaI, and HindIII, showed no differences in the digestion patterns of the seven gentamicin-resistance plasmids. The results supported the hypothesis that plasmid transfer between S. aureus and S. epidermidis occurs in nature.