The evolutionary histories of clinical and environmental SHV β-lactamases are intertwined.
The evolutionary histories of clinical and environmental SHV β-lactamases are intertwined.
复制标题
临床和环境SHV β-内酰胺酶的进化史是相互交织的。
DOI：
10.1007/s00239-013-9574-z
复制
发表时间：
2013
影响因子：
3.9
通讯作者：
Riley,MargaretA
中科院分区：
文献类型：
--
作者：
Dorit,RobertL;Roy,ChristopherM;Robinson,SandraM;Riley,MargaretA
抗生素耐药病原体的兴起使我们的注意力集中在抗生素耐药基因的来源上，在暴露于很少或没有抗生素的环境中这些基因的存在上，以及在临床中发现的耐药基因与在非临床环境中遇到的耐药基因之间的关系上。在这里，我们解决了一类耐药基因，SHV β-内酰胺酶的进化史。我们专注于从临床和非临床来源分离的blaSHVgenes，并表明临床上重要的耐药决定因素反复出现在环境中存在的blaSHVgenes的不同池中。虽然我们的研究结果反对所有临床衍生的blaSHV基因的单一共同起源的概念，但我们检测到在临床环境中塑造这种蛋白质的特征选择性签名。这种临床特征揭示了纯化和阳性选择对特定残基的联合作用，包括那些已知赋予广谱活性的残基。令人惊讶的是，从非临床环境中分离出来的抗生素耐药基因也经历了纯化和阳性选择的共同作用。出现的图片削弱了仅限于临床环境的抗生素耐药基因单独储存库的概念。相反，我们认为存在一个单一的广泛和可变的抗生素耐药基因库存在于环境中。
The rise of antibiotic-resistant pathogens focuses our attention on the source of antibiotic resistance genes, on the existence of these genes in environments exposed to little or no antibiotics, and on the relationship between resistance genes found in the clinic and those encountered in non-clinical settings. Here, we address the evolutionary history of a class of resistance genes, the SHV β-lactamases. We focus onblaSHVgenes isolated both from clinical and non-clinical sources and show that clinically important resistance determinants arise repeatedly from within a diverse pool ofblaSHVgenes present in the environment. While our results argue against the notion of a single common origin for all clinically derivedblaSHVgenes, we detect a characteristic selective signature shaping this protein in clinical environments. This clinical signature reveals the joint action of purifying and positive selection on specific residues, including those known to confer extended-spectrum activity. Surprisingly, antibiotic resistance genes isolated from non-clinical—and presumably antibiotic-free—settings also experience the joint action of purifying and positive selection. The picture that emerges undercuts the notion of a separate reservoir of antibiotic resistance genes confined only to clinical settings. Instead, we argue for the presence of a single extensive and variable pool of antibiotic resistance genes present in the environment.