Dataset Information

Assessment of Antibiotic Resistance and Efflux Pump Gene Expression in Neisseria Gonorrhoeae Isolates from South Africa by Quantitative Real-Time PCR and Regression Analysis.

ABSTRACT:

Introduction

Treatment of gonorrhoea infection is limited by the increasing prevalence of multidrug-resistant strains. Cost-effective molecular diagnostic tests can guide effective antimicrobial stewardship. The aim of this study was to correlate mRNA expression levels in Neisseria gonorrhoeae antibiotic target genes and efflux pump genes to antibiotic resistance in our population.

Methods

This study investigated the expression profile of antibiotic resistance-associated genes (penA, ponA, pilQ, mtrR, mtrA, mtrF, gyrA, parC, parE, rpsJ, 16S rRNA, and 23S rRNA) and efflux pump genes (macAB, norM, and mtrCDE), by quantitative real-time PCR, in clinical isolates from KwaZulu-Natal, South Africa. Whole-genome sequencing was used to determine the presence or absence of mutations.

Results

N. gonorrhoeae isolates, from female and male patients presenting for care at clinics in KwaZulu-Natal, South Africa, were analysed. As determined by binomial regression and ROC analysis, the most significant (p ≤ 0.05) markers for resistance prediction in this population, and their cutoff values, were determined to be mtrC (p = 0.024; cutoff <0.089), gyrA (p = 0.027; cutoff <0.0518), parE (p = 0.036; cutoff <0.0033), rpsJ (p = 0.047; cutoff <0.0012), and 23S rRNA (p = 0.042; cutoff >7.754).

Conclusion

Antimicrobial stewardship includes exploring options to conserve currently available drugs for gonorrhoea treatment. There is the potential to predict an isolate as either susceptible or nonsusceptible based on the mRNA expression level of specific candidate markers, to inform patient management. This real-time qPCR approach, with few targets, can be further investigated for use as a potentially cost-effective diagnostic tool to detect resistance.

SUBMITTER: Mitchev N

PROVIDER: S-EPMC9616671 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Assessment of Antibiotic Resistance and Efflux Pump Gene Expression in Neisseria Gonorrhoeae Isolates from South Africa by Quantitative Real-Time PCR and Regression Analysis.

Mitchev Nireshni N Singh Ravesh R Ramsuran Veron V Ismail Arshad A Allam Mushal M Kwenda Stanford S Mnyameni Florah F Garrett Nigel N Swe Swe-Han Khine K Niehaus Abraham J AJ Mlisana Koleka P KP

International journal of microbiology 20221021

<h4>Introduction</h4>Treatment of gonorrhoea infection is limited by the increasing prevalence of multidrug-resistant strains. Cost-effective molecular diagnostic tests can guide effective antimicrobial stewardship. The aim of this study was to correlate mRNA expression levels in <i>Neisseria gonorrhoeae</i> antibiotic target genes and efflux pump genes to antibiotic resistance in our population.<h4>Methods</h4>This study investigated the expression profile of antibiotic resistance-associated ge ...[more]

PMID: 36312786

Similar Datasets

Project description:Mosaic interspecifically acquired alleles of the multiple transferable resistance (mtr) efflux pump operon correlate with increased resistance to azithromycin in Neisseria gonorrhoeae in epidemiological studies. However, whether and how these alleles cause resistance is unclear. Here, we use population genomics, transformations, and transcriptional analyses to dissect the relationship between variant mtr alleles and azithromycin resistance. We find that the locus encompassing the mtrR transcriptional repressor and the mtrCDE pump is a hot spot of interspecific recombination introducing alleles from Neisseria meningitidis and Neisseria lactamica into N. gonorrhoeae, with multiple rare haplotypes in linkage disequilibrium at mtrD and the mtr promoter region. Transformations demonstrate that resistance to azithromycin, as well as to other antimicrobial compounds such as polymyxin B and crystal violet, is mediated through epistasis between these two loci and that the full-length mosaic mtrD allele is required. Gene expression profiling reveals the mechanism of resistance in mosaics couples novel mtrD alleles with promoter mutations that increase expression of the pump. Overall, our results demonstrate that epistatic interactions at mtr gained from multiple neisserial species has contributed to increased gonococcal resistance to diverse antimicrobial agents.IMPORTANCENeisseria gonorrhoeae is the sexually transmitted bacterial pathogen responsible for more than 100 million cases of gonorrhea worldwide each year. The incidence of resistance to the macrolide azithromycin has increased in the past decade; however, a large proportion of the genetic basis of resistance remains unexplained. This study is the first to conclusively demonstrate the acquisition of macrolide resistance through mtr alleles from other Neisseria species, demonstrating that commensal Neisseria bacteria are a reservoir for antibiotic resistance to macrolides, extending the role of interspecies mosaicism in resistance beyond what has been previously described for cephalosporins. Ultimately, our results emphasize that future fine-mapping of genome-wide interspecies mosaicism may be valuable in understanding the pathways to antimicrobial resistance. Our results also have implications for diagnostics and public health surveillance and control, as they can be used to inform the development of sequence-based tools to monitor and control the spread of antibiotic-resistant gonorrhea.

Dataset Information

Assessment of Antibiotic Resistance and Efflux Pump Gene Expression in Neisseria Gonorrhoeae Isolates from South Africa by Quantitative Real-Time PCR and Regression Analysis.

Introduction

Methods

Results

Conclusion

Publications

Assessment of Antibiotic Resistance and Efflux Pump Gene Expression in Neisseria Gonorrhoeae Isolates from South Africa by Quantitative Real-Time PCR and Regression Analysis.

Similar Datasets

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