A bovine myeloid antimicrobial peptide (BMAP-28) and its analogs kill pan-drug-resistant Acinetobacter baumannii by interacting with outer membrane protein A (OmpA).
A bovine myeloid antimicrobial peptide (BMAP-28) and its analogs kill pan-drug-resistant Acinetobacter baumannii by interacting with outer membrane protein A (OmpA).
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牛骨髓抗菌肽 (BMAP-28) 及其类似物通过与外膜蛋白 A (OmpA) 相互作用杀死泛耐药鲍曼不动杆菌
DOI：
10.1097/md.0000000000012832
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发表时间：
2018-10
期刊：
影响因子：
1.6
通讯作者：
Han J
中科院分区：
文献类型：
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作者：
Guo Y;Xun M;Han J
摘要抗菌肽具有多种抗菌活性。牛髓样抗菌肽（BMAP-28）属于cathelicidin衍生的抗菌肽，具有抗菌活性。由于泛耐药鲍曼不动杆菌（PDRAB）引起的感染和爆发数量迅速增加，我们试图确定BMAP-28及其4种类似肽（A837，A838，A839和A840）是否对PDRAB具有抗菌活性。此外，我们阐明了BMAP-28抑制PDRAB的可能机制。本研究通过最小抑菌浓度（MIC）分析和短期杀伤实验，检测了BMAP-28及其4个类似肽对PDRAB生长的抑制作用。我们还通过使用场发射扫描电子显微镜（FE-SEM）评估了BMAP-28及其类似物对细菌细胞表面的影响。为了探讨BMAP-28的抑制机制，我们研究了BMAP-28与外膜蛋白（OMPs）的相互作用，特别是BMAP-28与A.鲍曼不动杆菌OmpA（AbOmpA）是OMPs的主要成分，使用石英晶体微量天平（QCM）进行测定。BMAP-28及其4个类似物对PDRAB的生长有明显的抑制作用，并具有快速杀伤能力。与其他肽相比，BMAP-28对PDRAB显示出异常强烈和快速的抑制作用，并且还显示出对PDRAB的细胞表面造成损伤。此外，QCM分析提供了BMAP-28和AbOmpA之间潜在相互作用的证据。这些数据表明BMAP-28是治疗PDRAB感染的有希望的候选物，并且其抑制作用与其与AbOmpA的结合有关。
Abstract Antimicrobial peptides (AMPs) exhibit multiple activities against bacteria and fungi. A bovine myeloid antimicrobial peptide (BMAP-28) belongs to the cathelicidin-derived AMPs and has antimicrobial activity. Due to the rapidly increasing number of infections and outbreaks caused by pan-drug-resistant Acinetobacter baumannii (PDRAB), we sought to determine whether BMAP-28 and its 4 analog peptides (A837, A838, A839, and A840) have antimicrobial activity against PDRAB. Furthermore, we clarified the possible mechanism of inhibition by which of BMAP-28 acts against PDRAB. In the current study, we examined the inhibitory effect of BMAP-28 and its 4 analog peptides on the growth of PDRAB through minimal inhibitory concentration (MIC) analysis and short time killing assays. We also evaluated the effects of BMAP-28 and its analogs on the bacterial cell surface through the use of field emission scanning electron microscopy (FE-SEM). In order to determine the inhibitory mechanism of BMAP-28, we examined the interaction between BMAP-28 and outer membrane proteins (OMPs), especially the interaction between BMAP-28 and A. baumannii OmpA (AbOmpA), which is the main component of OMPs, by using a quartz crystal microbalance (QCM). BMAP-28 and its 4 analogs were effective in inhibiting the growth of PDRAB and had rapid killing ability. BMAP-28 showed exceptionally strong and rapid inhibitory effects on PDRAB when compared to the other peptides and was also shown to cause damage to the cell surface of PDRAB. Moreover, QCM analysis provided evidence of potential interaction between BMAP-28 and AbOmpA. These data indicate that BMAP-28 is a promising candidate for the treatment of PDRAB infections and that its inhibitory effects were related with its binding to AbOmpA.