Evaluation of an antimicrobial L-amino acid oxidase and peptide derivatives from Bothropoides mattogrosensis pitviper venom.

Evaluation of an antimicrobial L-amino acid oxidase and peptide derivatives from Bothropoides mattogrosensis pitviper venom.
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DOI:
10.1371/journal.pone.0033639
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Moreno SE
Moreno SE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Okubo BM;Silva ON;Migliolo L;Gomes DG;Porto WF;Batista CL;Ramos CS;Holanda HH;Dias SC;Franco OL;Moreno SE

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医疗保健相关感染 (HAI) 是全世界死亡和发病的原因。近年来,细菌对常见抗生素的耐药性普遍增加,突出表明需要开发新的替代品来控制这些病原体。毒蛇毒液由肽、蛋白质和无机成分的多方面混合物组成。 L-氨基氧化酶(LAO)是一种多功能酶,能够发挥包括抗菌活性在内的不同活性。在这项研究中,从Bothrops mattogrosensis (BmLAO) 中分离出一种新型LAO,并对其进行了生化表征。部分酶序列显示与Bothrops pauloensis LAO 完全同一。此外,此处分离的LAO对革兰氏阳性菌和阴性菌表现出显着的抗菌活性,清楚地表明其具有二级保护功能。除此之外,没有观察到针对巨噬细胞和红细胞的细胞毒活性。最后,合成了一些 LAO 片段(BmLAO-f1、BmLAO-f2 和 BmLAO-f3)并进行了进一步评估,也显示出增强的抗菌活性。肽片段是抗菌活性的关键残基,也通过理论模型进行了结构研究。这里报道的片段可能是合理设计可用于控制耐药微生物的新抗生素的有希望的候选者。
Healthcare-associated infections (HAIs) are causes of mortality and morbidity worldwide. The prevalence of bacterial resistance to common antibiotics has increased in recent years, highlighting the need to develop novel alternatives for controlling these pathogens. Pitviper venoms are composed of a multifaceted mixture of peptides, proteins and inorganic components. L-amino oxidase (LAO) is a multifunctional enzyme that is able to develop different activities including antibacterial activity. In this study a novel LAO from Bothrops mattogrosensis (BmLAO) was isolated and biochemically characterized. Partial enzyme sequence showed full identity to Bothrops pauloensis LAO. Moreover, LAO here isolated showed remarkable antibacterial activity against Gram-positive and -negative bacteria, clearly suggesting a secondary protective function. Otherwise, no cytotoxic activities against macrophages and erythrocytes were observed. Finally, some LAO fragments (BmLAO-f1, BmLAO-f2 and BmLAO-f3) were synthesized and further evaluated, also showing enhanced antimicrobial activity. Peptide fragments, which are the key residues involved in antimicrobial activity, were also structurally studied by using theoretical models. The fragments reported here may be promising candidates in the rational design of new antibiotics that could be used to control resistant microorganisms.
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