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利用淋病奈瑟菌基因组公共数据库检测与佐利氟达辛耐药相关的突变。

Using a public database of Neisseria gonorrhoeae genomes to detect mutations associated with zoliflodacin resistance.

作者信息

Adamson Paul C, Lin Eric Y, Ha Sung-Min, Klausner Jeffrey D

机构信息

Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

出版信息

J Antimicrob Chemother. 2021 Oct 11;76(11):2847-2849. doi: 10.1093/jac/dkab262.

Abstract

BACKGROUND

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an urgent global health threat. Zoliflodacin is a novel antibiotic undergoing clinical trials for the treatment of gonorrhoea. While there are limited data regarding zoliflodacin resistance in N. gonorrhoeae, three amino acid mutations have been associated with increased MICs of zoliflodacin.

OBJECTIVES

To determine the prevalence of three amino acid mutations associated with zoliflodacin resistance within a large, public database of nearly 13 000 N. gonorrhoeae genomes.

METHODS

PathogenWatch is an online genomic epidemiology platform with a public database of N. gonorrhoeae genomes. That database was used to extract gyrB sequence data and a Basic Local Alignment Search Tool (BLAST) search was performed to identify any of the three amino acid mutations in GyrB that are associated with increased zoliflodacin MICs: D429N, K450N or K450T. As a control for the search methodology, all GyrA sequences were also extracted and S91F mutations were identified and compared with the PathogenWatch database.

RESULTS

In total, 12 493 N. gonorrhoeae genomes from the PathogenWatch database were included. Among those genomes, none was identified that harboured any of the three mutations associated with increased zoliflodacin MICs. One genome was identified to have a mutation at position 429 in GyrB (D429V).

CONCLUSIONS

The findings suggest that the prevalence of the three mutations associated with zoliflodacin resistance in N. gonorrhoeae is very low. However, further research into the mechanisms of zoliflodacin resistance in N. gonorrhoeae is needed. Genomic epidemiology platforms like PathogenWatch can be used to enhance the global surveillance of AMR.

摘要

背景

淋病奈瑟菌的抗菌药物耐药性(AMR)是全球紧迫的健康威胁。佐利氟达辛是一种正在进行淋病治疗临床试验的新型抗生素。虽然关于淋病奈瑟菌对佐利氟达辛耐药性的数据有限,但三个氨基酸突变与佐利氟达辛的最低抑菌浓度(MIC)升高有关。

目的

在一个包含近13000个淋病奈瑟菌基因组的大型公共数据库中,确定与佐利氟达辛耐药性相关的三个氨基酸突变的流行情况。

方法

PathogenWatch是一个在线基因组流行病学平台,拥有淋病奈瑟菌基因组公共数据库。该数据库用于提取gyrB序列数据,并进行基本局部比对搜索工具(BLAST)搜索,以识别GyrB中与佐利氟达辛MIC升高相关的三个氨基酸突变中的任何一个:D429N, K450N或K450T。作为搜索方法的对照,还提取了所有GyrA序列,并识别S91F突变,并与PathogenWatch数据库进行比较。

结果

PathogenWatch数据库中总共纳入了12493个淋病奈瑟菌基因组。在这些基因组中,未发现携带与佐利氟达辛MIC升高相关的三个突变中的任何一个。鉴定出一个基因组在GyrB的429位有一个突变(D429V)。

结论

研究结果表明,淋病奈瑟菌中与佐利氟达辛耐药性相关的三个突变的流行率非常低。然而,需要对淋病奈瑟菌对佐利氟达辛耐药的机制进行进一步研究。像PathogenWatch这样的基因组流行病学平台可用于加强对AMR的全球监测。

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