摘要

抗生素抗性细菌对人类健康构成最大威胁。在世界卫生组织发布的此类细菌清单中，碳青霉烯类耐药鲍曼不动杆菌（几乎不存在任何治疗方法）位居榜首。鲍曼不动杆菌是最麻烦的ESKAPE病原体之一，其促进其作为成功病原体的上升的机制尚未得到很好的研究。在这方面的努力已经导致鉴定Hpa2-Ab，其是GNAT超家族的未表征的组蛋白乙酰转移酶。在这里，我们显示Hpa2-Ab使用表达Hpa2基因的大肠杆菌DH5α菌株赋予对氨基糖苷类抗生素的抗性。在CLSI-2010和KB测试的帮助下证明了氨基糖苷类抗生素的电阻率。 ITC，MALDI和乙酰化试验表明，赋予的抗性是进化抗生素乙酰化能力的结果。已知Hpa2使核分子乙酰化，然而在此发现它跨越其边界并参与其他功能。一系列生物化学和生物物理技术也被用于研究这种蛋白质，这表明Hpa2-Ab本质上本质上是寡聚体，主要作为二聚体存在，并且其界面主要通过疏水相互作用稳定。我们的工作展示了A. baumannii的进化生存策略，并提供了有助于其作为成功病原体上升的机制的见解。

Antibiotic-resistant bacteria pose the greatest threat to human health. Among the list of such bacteria released by WHO, carbapenem-resistant Acinetobacter baumannii , for which almost no treatment exists, tops the list. A. baumannii is one of the most troublesome ESKAPE pathogens and mechanisms that have facilitated its rise as a successful pathogen are not well studied. Efforts in this direction have resulted in identification of Hpa2- Ab, an uncharacterized histone acetyltransferase enzyme of GNAT superfamily. Here we show that Hpa2- Ab confers resistance against aminoglycoside antibiotics using E. coli DH5α strains in which Hpa2 gene is expressed. Resistivity for aminoglycoside antibiotics is demonstrated with the help of CLSI-2010 and KB tests. ITC, MALDI and acetylation assays indicate that conferred resistance is an outcome of evolved antibiotics acetylation capacity in this. Hpa2 is known to acetylate nuclear molecules however, here it is found to cross its boundary and participate in other functions. An array of biochemical and biophysical techniques were also used to study this protein, which demonstrate that Hpa2 -Ab is intrinsically oligomeric in nature, exists primarily as a dimer and its interface is mainly stabilized by hydrophobic interactions. Our work demonstrates an evolved survival strategy by  A. baumannii  and provides insights into the mechanism that facilitates it to rise as a successful pathogen.

https://www.ncbi.nlm.nih.gov/pubmed/30573651