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In vitro Susceptibility to β-Lactam Antibiotics and Viability of Neisseria gonorrhoeae Strains Producing Plasmid-Mediated Broad- and Extended-Spectrum β-Lactamases
Neisseria gonorrhoeae plasmids can mediate high-level antimicrobial resistance. The emergence of clinical isolates producing plasmid β-lactamases that can hydrolyze cephalosporins, the mainstay treatment for gonorrhea, may be a serious threat. In this work, N. gonorrhoeae strains producing plasmid-m...
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Published in: | Frontiers in microbiology 2022-06, Vol.13, p.896607-896607 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Neisseria gonorrhoeae
plasmids can mediate high-level antimicrobial resistance. The emergence of clinical isolates producing plasmid β-lactamases that can hydrolyze cephalosporins, the mainstay treatment for gonorrhea, may be a serious threat. In this work,
N. gonorrhoeae
strains producing plasmid-mediated broad- and extended-spectrum β-lactamases (ESBLs) were obtained
in vitro
, and their viability and β-lactam antibiotic susceptibility were studied. Artificial p
bla
TEM-1
and p
bla
TEM-20
plasmids were constructed by site-directed mutagenesis from a p
bla
TEM-135
plasmid isolated from a clinical isolate. Minimum inhibitory concentration (MIC) values for a series of β-lactam antibiotics, including benzylpenicillin, ampicillin, cefuroxime, ceftriaxone, cefixime, cefotaxime, cefepime, meropenem, imipenem, and doripenem, were determined. The
N. gonorrhoeae
strain carrying the p
bla
TEM-20
plasmid exhibited a high level of resistance to penicillins and second–fourth-generation cephalosporins (MIC ≥2 mg/L) but not to carbapenems (MIC ≤0.008 mg/L). However, this strain stopped growing after 6 h of culture. The reduction in viability was not associated with loss of the plasmid but can be explained by the presence of the plasmid itself, which requires additional reproduction costs, and to the expression of ESBLs, which can affect the structure of the peptidoglycan layer in the cell membrane. Cell growth was mathematically modeled using the generalized Verhulst equation, and the reduced viability of the plasmid-carrying strains compared to the non-plasmid-carrying strains was confirmed. The cell death kinetics of
N. gonorrhoeae
strains without the p
bla
TEM-20
plasmid in the presence of ceftriaxone can be described by a modified Chick–Watson law. The corresponding kinetics of the
N. gonorrhoeae
strain carrying the p
bla
TEM-20
plasmid reflected several processes: the hydrolysis of ceftriaxone by the TEM-20 β-lactamase and the growth and gradual death of cells. The demonstrated reduction in the viability of
N. gonorrhoeae
strains carrying the p
bla
TEM-20
plasmid probably explains the absence of clinical isolates of ESBL-producing
N. gonorrhoeae
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ISSN: | 1664-302X 1664-302X |
DOI: | 10.3389/fmicb.2022.896607 |