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赞比亚卢萨卡性传播感染门诊分离的淋病奈瑟菌的耐药性和异质性。

Antimicrobial resistance and heterogeneity of Neisseria gonorrhoeae isolated from patients attending sexually transmitted infection clinics in Lusaka, Zambia.

机构信息

Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, P.O. Box 50110, Zambia.

Department of Dermato-venereology, University Teaching Hospital, Lusaka, Zambia.

出版信息

BMC Genomics. 2024 Mar 18;25(1):290. doi: 10.1186/s12864-024-10155-y.

DOI:10.1186/s12864-024-10155-y
PMID:38500064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10949682/
Abstract

BACKGROUND

Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia.

METHODS

A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset.

RESULTS

The most frequent STs with 18.4% of isolates each were ST, ST and ST, followed by ST (13%), novel ST (7.9%), ST (7.9%), ST (5.3%), ST (5.3%), ST (2.6/%) and ST (2.6%) among the 38 genotyped isolates. The blaTeM-1B and tetM (55%) was the most prevalent combination of AMR genes, followed by blaTeM-1B (18.4%), tetM (15.8%), and the combination of blaTeM-1B, ermT, and tetL was 2.6% of the isolates. The AMR phenotypes were predicted in ciprofloxacin, penicillin, tetracycline, azithromycin, and cefixime. The combination of mutations 23.7% was gryA (S91F), parC (E91G), ponA (L421) and rpsJ (V57M), followed by 18.4% in gyrA (S91F), ponA (L421P), rpsJ (V57M), and 18.4% in gyrA (D95G, S91F), ponA (L421P), and rpsJ (V57M). The combinations in gyrA (D95G, S91F) and rpsJ (V57M), and gyrA (D95G, S91F), parC (E91F), ponA (L421P) and rpsJ (V57M) were 13.2% each of the isolates. Plasmid TEM-1 (84.2%), tetM (15.8%), and gonococcal genetic island (GGI) was detected in all isolates.

CONCLUSION

This study revealed remarkable heterogeneity of N. gonorrhoeae with bla, tetM, ponA, gyrA, and parC genes associated with high resistance to penicillin, tetracycline, and ciprofloxacin demanding revision of the standard treatment guidelines and improved antimicrobial stewardship in Zambia.

摘要

背景

淋病奈瑟菌的抗生素耐药性(AMR)对公共卫生构成威胁,因为菌株已经对用于治疗淋病的抗生素产生了耐药性。全基因组测序(WGS)可以检测和预测抗生素耐药性,从而增强淋病的控制和预防。赞比亚淋病奈瑟菌的分子流行病学数据很少。本研究旨在确定从 2019 年至 2020 年在赞比亚卢萨卡的性传播感染(STI)诊所就诊的患者中分离出的淋病奈瑟菌的遗传多样性。

方法

进行了一项横断面研究,对 2019 年至 2020 年期间从 122 名淋病患者中分离出的 38 株淋病奈瑟菌进行测序。通过 E 试验确定 AMR 谱,使用 NucliSens easyMaG 磁设备提取 DNA。在 Illumina NextSeq550 平台上进行全基因组测序。可在 https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 上获得的细菌分析管道(BAP)用于鉴定物种、组装基因组、多位点序列分型(MLST)、检测质粒和 AMR 基因。通过 CCphylo 数据集确定单核苷酸多态性(SNP)的系统发育。

结果

38 株基因分型分离株中最常见的 ST 分别为 ST、ST 和 ST,各占 18.4%,其次是 ST(13%)、新型 ST(7.9%)、ST(7.9%)、ST(5.3%)、ST(5.3%)、ST(2.6%)和 ST(2.6%)。AMR 基因最常见的组合是 blaTeM-1B 和 tetM(55%),其次是 blaTeM-1B(18.4%)、tetM(15.8%)和 blaTeM-1B、ermT 和 tetL 的组合占分离株的 2.6%。预测了 ciprofloxacin、penicillin、tetracycline、azithromycin 和 cefixime 的 AMR 表型。突变组合 23.7%为 gryA(S91F)、parC(E91G)、ponA(L421)和 rpsJ(V57M),其次是 gyrA(S91F)、ponA(L421P)、rpsJ(V57M)和 gyrA(D95G、S91F),占 18.4%。ponA(L421P)和 rpsJ(V57M),占 18.4%。gyrA(D95G、S91F)和 rpsJ(V57M)以及 gyrA(D95G、S91F)、parC(E91F)、ponA(L421P)和 rpsJ(V57M)的组合分别占分离株的 13.2%。所有分离株均检测到质粒 TEM-1(84.2%)、tetM(15.8%)和淋球菌遗传岛(GGI)。

结论

本研究揭示了淋病奈瑟菌的显著异质性,与青霉素、四环素和环丙沙星耐药性相关的 bla、tetM、ponA、gyrA 和 parC 基因,这需要修订标准治疗指南,并在赞比亚加强抗菌药物管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b165/10949682/50c1d5f09a6f/12864_2024_10155_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b165/10949682/51ba7a8ee9ed/12864_2024_10155_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b165/10949682/09d5f39b9cb5/12864_2024_10155_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b165/10949682/85c384382967/12864_2024_10155_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b165/10949682/50c1d5f09a6f/12864_2024_10155_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b165/10949682/51ba7a8ee9ed/12864_2024_10155_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b165/10949682/09d5f39b9cb5/12864_2024_10155_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b165/10949682/85c384382967/12864_2024_10155_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b165/10949682/50c1d5f09a6f/12864_2024_10155_Fig4_HTML.jpg

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