Intrinsic penicillin resistance in penicillinase-producing Neisseria gonorrhoeae strains
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1Department of Microbiology, Toho University School of Medicine, Tokyo.
Abstract:
The minimal inhibitory concentrations (MICs) of ampicillin for fifty strains of beta-lactamase-producing Neisseria gonorrhoeae (PPNG) isolated in Japan ranged from 1.56 to 200 micrograms/ml, and all the strains harbored a 4.5 megadalton plasmid. These strains were classified into two groups: dicloxacillin-susceptible (28%) and -resistant group (72%). A linear correlation was found in the dicloxacillin-susceptible strains between their beta-lactamase activity and the susceptibility to ampicillin, but not in the dicloxacillin-resistant strains. This suggests that the high ampicillin resistance in PPNG is due not only to acquiring the beta-lactamase producing plasmid, but also to some intrinsic resistance of the strains. To investigate a cause of the high ampicillin resistance, the beta-lactamase-producing plasmid, pTMS1, was transferred by conjugation to a penicillin-susceptible gonococcal strain as well as to its isogenic multiply antibiotic-resistant transformants, and the susceptibility of the transconjugants to ampicillin was determined. Acquisition of pTMS1 by a penicillin-susceptible strain resulted in a 32-fold increase in resistance to ampicillin, whereas the increase was 128-fold for its isogenic strains which contain some chromosomal mutations. These results suggest that reduced permeability of the outer membrane to ampicillin underlies the high ampicillin resistance of PPNG.
Insights
High ampicillin resistance in penicillin-resistant Neisseria gonorrhoeae (PPNG) is linked to both beta-lactamase plasmids and intrinsic strain resistance. Reduced outer membrane permeability contributes significantly to this resistance.
Area of Science:
- Microbiology
- Genetics
- Pharmacology
Background:
- Penicillin-resistant Neisseria gonorrhoeae (PPNG) strains exhibit high ampicillin resistance.
- These strains commonly harbor a 4.5 megadalton plasmid responsible for beta-lactamase production.
- PPNG strains can be classified based on susceptibility to dicloxacillin, indicating varying resistance mechanisms.
Purpose of the Study:
- To investigate the mechanisms underlying high ampicillin resistance in PPNG.
- To determine the role of the beta-lactamase-producing plasmid (pTMS1) and intrinsic strain factors in ampicillin resistance.
- To explore the contribution of outer membrane permeability to ampicillin resistance in PPNG.
Main Methods:
- Determining minimal inhibitory concentrations (MICs) of ampicillin for PPNG strains.
- Classifying PPNG strains based on dicloxacillin susceptibility.
- Transferring the pTMS1 plasmid via conjugation to susceptible and resistant gonococcal strains.
- Assessing ampicillin susceptibility of transconjugants.
Main Results:
- Ampicillin MICs for PPNG strains ranged from 1.56 to 200 µg/ml.
- A correlation between beta-lactamase activity and ampicillin susceptibility was observed in dicloxacillin-susceptible strains, but not in resistant strains.
- Transfer of pTMS1 increased ampicillin resistance by 32-fold in susceptible strains and 128-fold in strains with chromosomal mutations.
Conclusions:
- High ampicillin resistance in PPNG involves both plasmid-mediated beta-lactamase production and intrinsic resistance mechanisms.
- Reduced outer membrane permeability appears to be a key factor contributing to the significant ampicillin resistance observed in PPNG.
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