Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928-2013): antimicrobial use/misuse selects for resistance and drives evolution
Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928-2013): antimicrobial use/misuse selects for resistance and drives evolution
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DOI：
10.1186/s12864-020-6511-6
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发表时间：
2020-02-03
期刊：
影响因子：
4.4
通讯作者：
Unemo, Magnus
中科院分区：
文献类型：
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作者：
Golparian, Daniel;Harris, Simon R.;Unemo, Magnus
多药耐药淋病奈瑟菌菌株普遍存在，威胁着全球淋病治疗，而对淋球菌抗菌素耐药性（AMR）的出现、演变和传播的了解仍然有限。我们描述了淋球菌的基因组进化及其AMR，与引入抗微生物疗法有关，研究了丹麦1928年（抗生素前时代）至2013年的分离株。据我们所知，这是全球最古老的淋球菌收藏。方法对冻干分离株进行复活检测，采用Etest（18种抗菌素）和全基因组测序（WGS）进行检测。191株活菌和40株非活菌获得了质量保证的基因组序列，并采用多种系统基因组学方法进行了分析。结果淋球菌抗菌素耐药性，包括多种抗菌素耐药性决定因素的积累，特别是在20世纪50年代至70年代开始出现。到21世纪，对大多数抗菌素的耐药性很常见。尽管一些抗菌素耐药性决定因素影响许多生理功能和适应性，但抗菌素耐药性决定因素主要是由淋病治疗性抗菌素的使用/误用决定的。大多数抗菌素耐药性发生在属于一个多药耐药（MDR）分支的菌株中，该分支的基因组突变率高出近三倍。据推测，现代淋病奈瑟菌出现于16世纪晚期，其基因组随着时间的推移变得越来越保守。结论1928 - 2013年淋球菌WGS检测结果显示，在引入淋病治疗性抗菌药物前，除penB外，未检出AMR决定因子。现代淋球菌比以前假设的要年轻得多，并且在使用/误用抗菌剂的推动下，已经进化成一个更具克隆性的物种。应进一步研究耐多药淋球菌支系，以便早期发现有发展和维持耐多药倾向的菌株，并启动公共卫生干预措施。
Background Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR, related to the introduction of antimicrobial therapies, examining isolates from 1928 (preantibiotic era) to 2013 in Denmark. This is, to our knowledge, the oldest gonococcal collection globally. Methods Lyophilised isolates were revived and examined using Etest (18 antimicrobials) and whole-genome sequencing (WGS). Quality-assured genome sequences were obtained for 191 viable and 40 non-viable isolates and analysed with multiple phylogenomic approaches. Results Gonococcal AMR, including an accumulation of multiple AMR determinants, started to emerge particularly in the 1950s-1970s. By the twenty-first century, resistance to most antimicrobials was common. Despite that some AMR determinants affect many physiological functions and fitness, AMR determinants were mainly selected by the use/misuse of gonorrhoea therapeutic antimicrobials. Most AMR developed in strains belonging to one multidrug-resistant (MDR) clade with close to three times higher genomic mutation rate. Modern N. gonorrhoeae was inferred to have emerged in the late-1500s and its genome became increasingly conserved over time. Conclusions WGS of gonococci from 1928 to 2013 showed that no AMR determinants, except penB, were in detectable frequency before the introduction of gonorrhoea therapeutic antimicrobials. The modern gonococcus is substantially younger than previously hypothesized and has been evolving into a more clonal species, driven by the use/misuse of antimicrobials. The MDR gonococcal clade should be further investigated for early detection of strains with predispositions to develop and maintain MDR and for initiation of public health interventions.