Doherty Applied Microbial Genomics, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
Sex Transm Infect. 2018 Mar;94(2):151-157. doi: 10.1136/sextrans-2017-053287. Epub 2017 Dec 15.
Drug-resistant are now a global public health threat. Direct transmission of antibiotic-resistant gonococci between individuals has been proposed as a driver for the increased transmission of resistance, but direct evidence of such transmission is limited. Whole-genome sequencing (WGS) has superior resolution to investigate outbreaks and disease transmission compared with traditional molecular typing methods such as multilocus sequence typing (MLST) and multiantigen sequence (NG-MAST). We therefore aimed to systematically investigate the transmission of between men in sexual partnerships using WGS to compare isolates and their resistance to antibiotics at a genome level.
458 couples from a large prospective cohort of men who have sex with men (MSM) tested for gonorrhoea together between 2005 and 2014 were included, and WGS was conducted on all isolates from couples where both men were culture-positive for . Resistance-determining sequences were identified from genome assemblies, and comparison of isolates between and within individuals was performed by pairwise single nucleotide polymorphism and pangenome comparisons, and in silico predictions of NG-MAST and MLST.
For 33 of 34 (97%; 95% CI 85% to 100%) couples where both partners were positive for gonorrhoea, the resistance-determining genes and mutations were identical in isolates from each partner (94 isolates in total). Resistance determinants in isolates from 23 of 23 (100%; 95% CI 86% to 100%) men with multisite infections were also identical within an individual. These partner and within-host isolates were indistinguishable by NG-MAST, MLST and whole genomic comparisons.
These data support the transmission of antibiotic-resistant strains between sexual partners as a key driver of resistance rates in gonorrhoea among MSM. This improved understanding of the transmission dynamics of between sexual partners will inform treatment and prevention guidelines.
耐药菌株现在是全球公共卫生威胁。已经有人提出，耐抗生素淋球菌在个体之间的直接传播是耐药性传播增加的一个驱动因素，但这种传播的直接证据有限。与传统的分子分型方法（如多位点序列分型（MLST）和多抗原序列（NG-MAST）相比，全基因组测序（WGS）具有更高的分辨率，可以用于调查暴发和疾病传播。因此，我们旨在使用 WGS 系统地研究性伴侣之间淋球菌的传播，以在基因组水平上比较分离株及其对抗生素的耐药性。
2005 年至 2014 年间，对一个大型男男性行为者（MSM）前瞻性队列中的 458 对夫妇进行了淋病共同检测，对所有培养阳性的夫妇中的分离株进行了 WGS。从基因组组装中鉴定出耐药决定序列，并通过成对单核苷酸多态性和泛基因组比较，以及 NG-MAST 和 MLST 的计算机预测，对个体内和个体间的分离株进行比较。
在 34 对（97%；95%可信区间 85%至 100%）中，当双方都感染淋病时，33 对（97%；95%可信区间 85%至 100%）夫妇中，来自每个伴侣的分离株中的耐药决定基因和突变是相同的（总共 94 个分离株）。在 23 对（100%；95%可信区间 86%至 100%）多部位感染男性的分离株中，耐药决定因素在个体内也是相同的。这些伴侣和个体内分离株在 NG-MAST、MLST 和全基因组比较中无法区分。
这些数据支持耐抗生素菌株在性伴侣之间的传播是导致 MSM 淋病耐药率的一个关键驱动因素。对淋球菌在性伴侣之间传播动力学的这种更好理解将为治疗和预防指南提供信息。
