In silico serine β-lactamases analysis reveals a huge potential resistome in environmental and pathogenic species
In silico serine β-lactamases analysis reveals a huge potential resistome in environmental and pathogenic species
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DOI：
10.1038/srep43232
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发表时间：
2017-02-24
影响因子：
4.6
通讯作者：
Makarewicz, Oliwia
中科院分区：
文献类型：
--
作者：
Brandt, Christian;Braun, Sascha D.;Makarewicz, Oliwia
抗菌化合物的分泌是一种古老的机制，对于与其他微生物竞争的微生物具有明显的生存益处。因此，赋予耐药性的机制也是古老的，可能代表了环境细菌中被低估的储存库。在这种情况下，β-内酰胺酶（BL）由于其在医院环境中的长期存在和多样化而受到极大关注，导致出现对头孢菌素（超广谱BL = ESBL）和碳青霉烯类（碳青霉烯酶）具有耐药性的革兰氏阴性病原体。在目前的研究中，蛋白质序列数据库被用来分析BL，结果显示了大量的未知和功能不明的BL在众多的环境和致病物种。总之，这些BL代表了潜在可转移抗性基因的未表征的储存库。考虑到所有可用数据，计算机模拟方法似乎比有限数据集的分析更充分地反映了给定的耐药基因组。这种方法导致了一个更精确的定义BL进化枝和保守的图案。此外，它可以支持新的耐药决定因素的预测，并改善稳健的分子诊断的定制开发。
The secretion of antimicrobial compounds is an ancient mechanism with clear survival benefits for microbes competing with other microorganisms. Consequently, mechanisms that confer resistance are also ancient and may represent an underestimated reservoir in environmental bacteria. In this context, beta-lactamases (BLs) are of great interest due to their long-term presence and diversification in the hospital environment, leading to the emergence of Gram-negative pathogens that are resistant to cephalosporins (extended spectrum BLs = ESBLs) and carbapenems (carbapenemases). In the current study, protein sequence databases were used to analyze BLs, and the results revealed a substantial number of unknown and functionally uncharacterized BLs in a multitude of environmental and pathogenic species. Together, these BLs represent an uncharacterized reservoir of potentially transferable resistance genes. Considering all available data, in silico approaches appear to more adequately reflect a given resistome than analyses of limited datasets. This approach leads to a more precise definition of BL clades and conserved motifs. Moreover, it may support the prediction of new resistance determinants and improve the tailored development of robust molecular diagnostics.