Stable antibiotic resistance and rapid human adaptation in livestock-associated MRSA
Stable antibiotic resistance and rapid human adaptation in livestock-associated MRSA
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DOI：
10.1101/2021.08.20.457141
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发表时间：
2021-08
期刊：
影响因子：
7.7
通讯作者：
M. Matuszewska;Gemma G. R. Murray;X. Ba;Rhiannon M Wood;M. Holmes;L. Weinert
中科院分区：
文献类型：
--
作者：
M. Matuszewska;Gemma G. R. Murray;X. Ba;Rhiannon M Wood;M. Holmes;L. Weinert
可移动遗传元件(MGES)是细菌中水平基因转移的媒介，但也可以被子细胞垂直遗传。建立导致细菌基因组中MGES当代模式的动力学是预测新的和耐药病原体的出现和进化的核心。耐甲氧西林金黄色葡萄球菌(MRSA)克隆复合体(CC)398是欧洲牲畜中的主要MRSA，也是人类感染的日益严重的原因。以前的研究已经确定了三类MGE，它们的存在或不存在将与牲畜相关的CC398与密切相关且对抗生素抗药性较低的人类相关群体区分开来。在这里，我们使用了27年来从牲畜和人类中采集的1180个CC398基因组的集合，全面描述了这些MGES的进化动力学。我们发现，与家畜相关的CC398的出现与携带四环素抗性基因的Tn916转座子的获得是一致的，该基因已稳定遗传了57年。紧随其后的是携带甲氧西林、四环素和重金属抗性基因的V型SCCmec，这种基因已经保持了35年，偶尔会被截断和替换为IV型SCCmec。相比之下，携带人类免疫逃避基因簇的一类前驱噬菌体在与牲畜相关的CC398中基本上不存在，在与人和牲畜相关的CC398中反复获得和丢失。这些截然不同的动态意味着，当牲畜相关的MRSA传播给人类时，对人类宿主的适应超过了抗生素耐药性的丧失。此外，与耐药性相关的MGES的稳定遗传表明，欧洲农场抗生素和氧化锌使用量的持续减少对家畜相关的MRSA的影响将缓慢实现。
Mobile genetic elements (MGEs) are agents of horizontal gene transfer in bacteria, but can also be vertically inherited by daughter cells. Establishing the dynamics that led to contemporary patterns of MGEs in bacterial genomes is central to predicting the emergence and evolution of novel and resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) clonal-complex (CC) 398 is the dominant MRSA in European livestock and a growing cause of human infections. Previous studies have identified three categories of MGEs whose presence or absence distinguishes livestock-associated CC398 from a closely related and less antibiotic-resistant human-associated population. Here we fully characterise the evolutionary dynamics of these MGEs using a collection of 1,180 CC398 genomes, sampled from livestock and humans, over 27 years. We find that the emergence of livestock-associated CC398 coincided with the acquisition of a Tn916 transposon carrying a tetracycline resistance gene, which has been stably inherited for 57 years. This was followed by the acquisition of a type V SCCmec that carries methicillin, tetracycline and heavy metal resistance genes, which has been maintained for 35 years, with occasional truncations and replacements with type IV SCCmec. In contrast, a class of prophages that carry a human immune evasion gene cluster and that are largely absent from livestock-associated CC398, have been repeatedly gained and lost in both human- and livestock-associated CC398. These contrasting dynamics mean that when livestock-associated MRSA is transmitted to humans, adaptation to the human host outpaces loss of antibiotic resistance. In addition, the stable inheritance of resistance-associated MGEs suggests that the impact of ongoing reductions in antibiotic and zinc oxide use in European farms on livestock-associated MRSA will be slow to be realised.