TEM-1β-内酰胺酶的自然进化：实验重建和临床意义。,FEMS Microbiology Reviews

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TEM-1β-内酰胺酶的自然进化：实验重建和临床意义。
FEMS Microbiology Reviews ( IF 10.1 ) Pub Date : 2010-04-24 , DOI: 10.1111/j.1574-6976.2010.00222.x
Merijn L M Salverda ₁ , J Arjan G M De Visser , Miriam Barlow

Affiliation

TEM-1β-内酰胺酶是周围最著名的抗生素耐药性决定因素之一。它赋予了对青霉素和早期头孢菌素的抗性，并且由于引入了源自这些抗生素的新药而显示出惊人的功能可塑性。自1960年代发现以来，全世界医院和诊所已经分离出170多种TEM-1变体，这些变体具有不同的氨基酸序列，通常具有抗性表型。除了这种有据可查的“自然”进化，TEM-1的体外进化已成为许多实验研究的焦点。在这篇综述中，我们比较了TEM-1的自然进化和实验室进化，以解决这个问题，即在多大程度上可以重复抗生素抗性的进化，因此可能是可以预测的，在实验室条件下。我们还使用该比较来深入了解临床分离物中迄今尚未表征的替代的适应性相关性，并预测自然界中尚未观察到的替代。基于新的结构见解，我们回顾了有关TEM-1中有助于其抗性表型扩展的取代的已知信息。最后，我们讨论了过去十年中TEM等位基因的临床相关性，该相关性主要由另一种β-内酰胺酶CTX-M的出现所主导。我们回顾了关于TEM-1中有助于其抗性表型扩展的取代的已知信息。最后，我们讨论了过去十年中TEM等位基因的临床相关性，这一相关性主要由另一种β-内酰胺酶CTX-M的出现所主导。我们回顾了关于TEM-1中有助于其抗性表型扩展的取代的已知信息。最后，我们讨论了过去十年中TEM等位基因的临床相关性，这一相关性主要由另一种β-内酰胺酶CTX-M的出现所主导。

"点击查看英文标题和摘要"

Natural evolution of TEM-1 β-lactamase: experimental reconstruction and clinical relevance.

TEM-1 β-lactamase is one of the most well-known antibiotic resistance determinants around. It confers resistance to penicillins and early cephalosporins and has shown an astonishing functional plasticity in response to the introduction of novel drugs derived from these antibiotics. Since its discovery in the 1960s, over 170 variants of TEM-1 - with different amino acid sequences and often resistance phenotypes - have been isolated in hospitals and clinics worldwide. Next to this well-documented 'natural' evolution, the in vitro evolution of TEM-1 has been the focus of attention of many experimental studies. In this review, we compare the natural and laboratory evolution of TEM-1 in order to address the question to what extent the evolution of antibiotic resistance can be repeated, and hence might have been predicted, under laboratory conditions. We also use the comparison to gain an insight into the adaptive relevance of hitherto uncharacterized substitutions present in clinical isolates and to predict substitutions not yet observed in nature. Based on new structural insights, we review what is known about substitutions in TEM-1 that contribute to the extension of its resistance phenotype. Finally, we address the clinical relevance of TEM alleles during the past decade, which has been dominated by the emergence of another β-lactamase, CTX-M.

更新日期：2010-11-01

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