Conjugative plasmids in MRSA.
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Plasmids↗
Biomedical subjects
D E Townsend
Publications and source records attributed to D E Townsend.
A plasmid for diffusible pigment production in Staphylococcus aureus.
Production of diffusible pigment in a strain of Staphylococcus aureus (WG260) has been associated with a plasmid of c.26 megadaltons which can be co-transduced with inducible erythromycin and spectinomycin resistance. However, the diffusible pigment plasmid can be lost from the transductants without loss of inducible erythromycin and spectinomycin resistance. The evidence suggests that the resistance determinants are located on an element similar or identical to transposon Tn554, and, during transduction of the diffusible pigment plasmid, a copy of the resistance determinants always inserts into the chromosome of the transductant. This is the first report of such an element occurring on a plasmid in a clinical isolate of S. aureus. To date, the diffusible pigment plasmid has been isolated only as the open-circular conformation of plasmid DNA and is probably a highly relaxable plasmid. The production of the orange, diffusible pigment was shown to be independent of colony pigmentation.
Chromosome Mapping↗
A conjugative plasmid encoding production of a diffusible pigment and resistance to aminoglycosides and macrolides in Staphylococcus aureus.
A methicillin-resistant strain of Staphylococcus aureus, WG512, was isolated in 1968 and has been shown to harbour a plasmid, pWG14, which encodes the production of a diffusible pigment and resistance to kanamycin, neomycin, streptomycin, lincomycin, erythromycin and spectinomycin. Plasmid pWG14 has only been detected as a slowly migrating band of DNA during agarose-gel electrophoresis, and this was thought to be the open-circular form of the plasmid with an estimated molecular weight of 30-34 Mdal. The transfer properties of this plasmid were compared with a non-conjugative plasmid encoding tetracycline resistance and the class 2, conjugative plasmid described by Archer and Johnston (1983). Plasmid pWG14 shared many of the conjugative properties of the latter plasmid, including the ability to transfer at high frequency on the surface of a filter membrane and to transfer between non-lysogenic strains in the absence of Ca++ and in the presence of citrate of DNase I. However, unlike the class 2 plasmid, pWG14 was able to transfer in broth culture at low frequency and did not mobilise the non-conjugative plasmid. Furthermore, the class 2 plasmid and pWG14 were shown to belong to different incompatibility groups. A derivative of WG512, which had lost the ability to produce the diffusible pigment along with plasmid pWG14 but had retained the resistance determinants of plasmid pWG14 in the chromosome, was used to demonstrate that the conjugative mechanism of pWG14 was a property of the plasmid and not the resistance determinants.
Aminoglycosides↗
Distribution of plasmid-borne resistance to nucleic acid binding compounds in methicillin-resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) which are epidemic in Australian hospitals have been found to be genetically different from strains previously isolated in Australia and in Europe. A characteristic feature of the recent Australian isolates is a plasmid which encodes resistance to nucleic acid binding compounds (NAB) such as propamidine isethionate. Of 753 MRSA strains isolated from around the world in 1980-1983, c. 60% were NAB resistant. The determinant for this resistance could be transferred from 90% of strains to a recipient strain in mixed culture. A plasmid analysis revealed that, in general, the largest plasmid of MRSA isolates coded for NAB resistance and may carry other determinants for penicillinase production and resistance to gentamicin, trimethoprim, neomycin, tetracycline, cadmium and mercury. Some plasmids exhibited unusual behaviour with the appearance of deletion mutants after transfer and, in one case, a high-frequency alteration in the expression of gentamicin resistance from high-level to low-level resistance, correlated to a deletion of c. 0.5 megadalton of plasmid DNA. These results demonstrate that these NAB-resistance plasmids are not unique to Australian MRSA strains but are widely distributed throughout the world.
Benzamidines↗
Evolution of Australian isolates of methicillin-resistant Staphylococcus aureus: a problem of plasmid incompatibility?
Methicillin-resistant Staphylococcus aureus (MRSA), currently causing problems in Australian hospitals, have chromosomal penicillinase and carry a new family of incompatibility group I (IncI) plasmids that encode resistance to nucleic acid-binding compounds (NAB). These plasmids may carry additional determinants for penicillinase production and resistance to gentamicin and trimethoprim. By comparison, earlier MRSA isolates from Australia were NAB-sensitive and the penicillinase determinants were carried on IncI plasmids. The possibility that these newer MRSA isolates have the same 'clonal' origin as other MRSA isolates has been investigated. Forcible maintenance of IncI penicillinase plasmids and NAC-resistance plasmids in the same cells resulted in various recombination events. Similar recombination events to those generated in the laboratory have been found in MRSA isolates.
Australia↗
A resistance determinant to nucleic acid-binding compounds in methicillin-resistant Staphylococcus aureus.
Recent isolates of methicillin-resistant Staphylococcus aureus from Australia and several other countries carry a plasmid coding for high levels of resistance to propamidine isethionate and low levels of resistance to cetyltrimethyl-ammonium bromide. The reasons for the acquisition and retention of such a determinant are not known. To define the properties of this resistance determinant in more detail, the minimum inhibitory concentrations of a series of cationic agents, including ethidium bromide, were determined and a cationic-resistance profile prepared for several strains of S. aureus and their isogenic, sensitive derivatives. The compounds for which resistance is coded by this determinant all bind to nucleic acids. Hence the determinant has been designated the NAB (nucleic acid-binding compounds)-resistance determinant.
Amidines↗
Transfer of plasmid-borne aminoglycoside-resistance determinants in staphylococci.
Aminoglycoside-resistance determinants in staphylococci are borne on conjugative and non-conjugative plasmids. The conjugative plasmids were found in methicillin-resistant strains of Staphylococcus aureus isolated recently in Darwin and Sydney, Australia and in Houston, Texas, USA. These plasmids and the class-2 conjugative plasmid reported by Archer and Johnston (1983) had similar patterns of EcoR1 restriction-endonuclease fragments, encoded resistance to gentamicin, kanamycin and neomycin, transferred to a non-lysogenic recipient in conditions that promoted close cell-to-cell contact and mobilised a small, non-conjugative plasmid. A further plasmid, pWG14, encoding resistance to kanamycin, neomycin, streptomycin, erythromycin and lincomycin, also displayed conjugative properties but did not mobilise the small, non-conjugative plasmid. The transfer frequency of all conjugative plasmids was stimulated by the addition of polyethylene glycol, particularly at concentrations above 20%, to mixtures of donor and recipient broth cultures. Polyethylene glycol appeared to promote close cell-to-cell contact between donor and recipient cells. A representative of the most common aminoglycoside-resistance plasmids in Australian isolates of methicillin-resistant S. aureus was non-conjugative and transferred by a bacteriophage-mediated system to a lysogenic recipient. With the exception of plasmid pWG14, the conjugative plasmids were also transferred by a bacteriophage-mediated system. Furthermore, cultural conditions that favoured conjugative transfer of plasmids inhibited bacteriophage-mediated transfer and vice versa. The efficacy of the two transfer systems for analysing the plasmids of gentamicin-resistant, methicillin-resistant isolates of S. aureus has been compared.
Aminoglycosides↗
"Australian" methicillin-resistant Staphylococcus aureus in a London hospital?
The Royal Free Hospital in London has experienced the spread of a phage 85 methicillin-resistant Staphylococcus aureus (MRSA). An analysis of a sample has demonstrated that the plasmids carried by these strains, and the type and location of their drug-resistance determinants, are similar to those of MRSA strains which have been causing problems in some Australian hospitals.
Australia↗
Structural anomalies of the cervix and vagina in women enrolled in the Diethylstilbestrol Adenosis (DESAD) Project.
Among women exposed in utero to diethylstilbestrol (DES) and enrolled in the Diethylstilbestrol Adenosis (DESAD) Project, structural anomalies of the cervix or vagina were found in 25% of the 1,655 subjects identified by review of prenatal records, 43% of the 800 who themselves requested entry into the project, and 49% of the 1,089 referred by physicians but in only 2% of the 963 control subjects. Among the 367 cases found by record review to have complete information on the DES exposure, multivariate analysis indicated close association of the anomalies with the gestational week of first exposure and the total dose. Also, the prevalence rate of the anomalies was lower among subjects who had been pregnant and higher among those with later age at menarche.
Abnormalities, Drug-Induced↗
Treatment of vulvar carcinoma in situ with the CO2 laser.
Between January 1960 and December 1982, 142 patients with carcinoma in situ of the vulva were treated at Cedars-Sinai Medical Center and UCLA Medical Center. Primary treatment consisted of wide excision in 45 patients; vulvectomy in 23 patients; topical chemotherapy in 9 patients; and CO2 laser therapy in 42 patients. Twenty-three patients were also treated with the CO2 laser for recurrent disease. Multifocal disease was present in 59% of the cases. Lesions involving the posterior vulva recurred most commonly, for both initial and recurrent disease. Results utilizing the CO2 are compared with the other methods of treating carcinoma in situ of the vulva. The CO2 laser is well suited for treatment of both multifocal and unifocal vulvar lesions, as it allows for maximal retention of vulvar integrity with no decrease in therapeutic efficacy.
Adult↗
A pilot study of lorazepam-induced amnesia with cis-platinum-containing chemotherapy.
Eighteen patients with advanced epithelial ovarian cancer were given 36 courses of cis-platinum-containing chemotherapy at Cedars-Sinai Medical Center. Patients were given lorazepam (Ativan) prior to chemotherapy. Amnesia for the day of chemotherapy was reported in 29 courses. Lack of recall for the chemotherapy infusion and the subsequent 8 hr or greater was reported in 33 of the 36 courses. In two courses, no amnesia effects were noted. No serious side effects of lorazepam therapy occurred and all patients believed that the amnesic effect was beneficial during chemotherapy. Lorazepam (Ativan) appears to be a safe medication to induce amnesia for cis-platinum chemotherapy and deserves further study to determine its effect on anticipatory vomiting, nausea and vomiting, and patient compliance with continued chemotherapy.
Adult↗
Genetic analysis of methicillin-resistant Staphylococcus aureus from a Western Australian hospital.
The isolates from an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) at Royal Perth Hospital (RPH) during a 3 month period in 1982 have been compared genetically with MRSAs isolated at the same hospital during 1969-1973. The 1982 isolates are genetically similar to isolates from eastern Australia and appear to have been introduced by a patient transferred from a hospital in another Australian state. Methicillin-resistant Staph. aureus isolated during 1969-1973 were genetically distinguishable from the 1982 isolates but were similar to strains reported from elsewhere in the world during these years. This indicates that the MRSA strains currently prevalent in Australia are either a new type or are related to previous MRSAs but have undergone considerable genetic change. These results give further support to suggestions that the strains of MRSA currently being isolated in Australian hospitals have special properties which have facilitated their spread.
Australia↗
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.
DNA Restriction Enzymes↗
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.
Benzamidines↗
Plasmid-mediated resistance to quaternary ammonium compounds in methicillin-resistant Staphylococcus aureus.
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Humans↗
Maturation of vaginal and cervical epithelium in women exposed in utero to diethylstilbestrol (DESAD Project).
A total of 452 women with documented exposure in utero to diethylstilbestrol (DES) with epithelial findings present at the time of their initial examination have been evaluated prospectively to determine whether these findings changed over a period of 3 years. The examinations were all performed according to a strict protocol. Findings present at the time of the third annual examination were verified at a fourth examination. A verified decrease in the extent of epithelial findings occurred in 29.2% of these women and a verified increase in 6.6%; 53.1% had no change in the extent of epithelial findings, and 11.1% had a change that could not be verified at the time of the fourth visit. Analysis of many variables failed to identify a strong association between any variable and a decrease in the extent of the findings. It appears that the most important factor in the occurrence of changes in DES-associated findings is the passage of time.
Adolescent↗
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.
Australia↗