Plasmid-Mediated Beta-Lactamase Production in Neisseria gonorrhoeae

Abstract

Several 8-lactamase-producing, penicillin-resistant strains of Neisseria gonorrhoeae were examined for R plasmids. Penicillin-resistant strains isolated from men returning from the Far East and their contacts contained a 4.4 x 106-dalton plasmid in common. Transformation studies and the isolation of a spontaneous penicillin-susceptible segregant showed that the structural gene for f8-lactamase was part of the 4.4 x 106-dalton plasmid. An additional penicillinresistant gonococcal strain isolated in London was found to harbor a 3.2 x 106-dalton R plasmid. Deoxyribonucleic acid (DNA)-DNA duplex studies revealed that the penicillin-resistant gonococcal isolates contained a significant portion (about 40%) of the transposable DNA sequence, TnA, which includes the f8-lactamase gene commonly found on R plasmids of the Enterobacteriaceae and Haemophilus influenzae.It has been known for some time that the R plasmids of enteric species enjoy a very broad host range (1,14). The recent finding (reviewed in 4, 6, 28) that certain pIa'smid-mediated antibiotic resistance genes reside upon discrete sequences of deoxyribonucleic acid (DNA) that have the capacity to transpose from plasmid to plasmid has further demonstrated that the range ofplasmid-mediated antibiotic resistance genes might be even broader than that of the whole plasmid genome. Therefore, plausible mechanisms exist by which pathogenic microorganisms, previously antibiotic susceptible, may be converted to stable antibiotic resistance by the direct extension of an entire R plasmid or by the simple addition of only a segment of DNA to a preexisting indigenous plasmid gene pool (6,15,19).Previous studies from this lAboratory (21) and others (3, 24, 30) have established that most strains of Neisseria gonorrhoeae contain plasmid species that are cryptic in the phenotypic sense. For example, our examination of30 antibiotic-susceptible gonococcal isolates showed that 28 strains harbored a multicopy (2.6 + 6.2) x 106--dalton (2.6 MDal) plasmid, and 1 strain contained a 24.5-MDal plasmid species, whereas 1 strain was plasmid free (13; L. P. Elwell and S. Falkow, in R. Roberts, ed., The Gonococcus, in press). The demonstration of a widespread plasmid gene pod in gonococci together with the emergence, epidemiology, and molecular nature of R plasmids mediating ampicillin resistance in Haemophilus influenzae (11, 12) led us to speculate (15) that gonococci were likely candidates to acquire plasmidmediated penicillin resistance specified by a (8-lactamase. Consequently, the recent isolation of f8-lactamase-producing strains of N. gonbrrhoeae (2, 25, 26) prompted us to examine them for the presence of a novel DNA species that might represent an R plasmid.In this study we report the detection of plasmid species from three penicillin-resistant clinical isolates of N. gonorrhoeae. We furher demonstrate that these plasmids probably represent a direct or indirect extension of the plasmid gene pool of enteric species to gonococci.

Plasmid-Mediated Ampicillin Resistance in Haemophilus ducreyi

“…Three strains were resistant to ampicillin (minimal inhibitory concentration > 128 ,ug/ml) and produced /8-lactamase as determined by hydrolysis of a chromogenic cephalosporin (23). Since plasmid-mediated 83-lactamase production had been documented in Haemophilus influenzae (10) and Neisseria gonorrhoeae (2,11,26), we wondered if f8-lactamase production might also be plasmid mediated in H. ducreyi and whether there might be any relationship between such a plasmid and the previously characterized plasmids of N. gonorrhoeae and H. influenzae.…”

The new hospital epidemiology

“…ducreyi from world wide sources are similar and moreover have sequences in common with /Mactamase plasmids in N. gonorrhoeae (Brunton et al 1982). The overall plasmid profiles of many /Mactamase producing N. gonorrhoeae are different; but, since cryptic plasmids are also present, Elwell et al (1977) suggested that insertion of gene sequences into pre-existing plasmids may have occurred. They further speculate that some fragments of DNA could prove exceptionally mobile and, as the extrachromosomal gene pool increases, plasmids with wider abilities to infect diverse groups of organisms will arise and be maintained.…”

Understanding the contribution of environmental factors in the spread of antimicrobial resistance

“…Multiple drug resistance emerged a few years later in the 1950s to early 1960s among several gastrointestinal/foodborne pathogens including Escherichia coli, Shigella and Salmonella (FBI) [17]. Multiple drugs resistance has continued to spread among common pathogens, with Haemophilus influenzae developing resistance to ampicillin [18], chloramphenicol and tetracycline [19,20] and an increased resistance to ampicillin observed, with ampicillin-resistant Neisseria gonorrhoea (STI) emerging mainly in developed countries in the 1970s [9,21]. Currently, all WHO regions report very high rates of resistance amongst common bacteria (for e.g.…”