Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus.
Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus.
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DOI：
10.1038/srep29707
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发表时间：
2016-07-11
影响因子：
4.6
通讯作者：
Seleem MN
中科院分区：
文献类型：
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作者：
Mohamed MF;Abdelkhalek A;Seleem MN
耐甲氧西林金黄色葡萄球菌（MRSA）感染提出了一个严重的挑战，因为出现耐药性的许多传统抗生素。由于其独特的作用方式，抗菌肽是传统抗生素的新型替代品，用于解决细菌的多药耐药性问题。在此，我们研究了两种短的新肽（WR 12，一种仅由精氨酸和色氨酸组成的12个残基的肽，和D-IK 8，一种8个残基的β折叠肽）对多药耐药葡萄球菌的抗菌活性。体外抗菌试验表明，两种肽对耐甲氧西林金黄色葡萄球菌（MRSA）、万古霉素耐药链球菌（S。金黄色葡萄球菌、利奈唑胺耐药S.金黄色葡萄球菌和耐甲氧西林葡萄球菌。表皮。与万古霉素和利奈唑胺相比，WR 12和D-IK 8能够根除持续存在的MRSA（处于稳定生长期），并显示出对细胞内MRSA的显著清除。在体内，局部WR 12和D-IK 8显著降低MRSA感染皮肤病变中的细菌负荷和促炎细胞因子水平，包括肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）。此外，这两种肽破坏了体外建立的S.金黄色葡萄球菌和epidermidis显著高于测试的传统抗微生物剂。总之，这些结果支持WR 12和D-IK 8用作治疗葡萄球菌皮肤感染的局部抗微生物剂的潜力。
Methicillin-resistant Staphylococcus aureus (MRSA) infections present a serious challenge because of the emergence of resistance to numerous conventional antibiotics. Due to their unique mode of action, antimicrobial peptides are novel alternatives to traditional antibiotics for tackling the issue of bacterial multidrug resistance. Herein, we investigated the antibacterial activity of two short novel peptides (WR12, a 12 residue peptide composed exclusively of arginine and tryptophan, and D-IK8, an eight residue β-sheet peptide) against multidrug resistant staphylococci. In vitro, both peptides exhibited good antibacterial activity against MRSA, vancomycin-resistant S. aureus, linezolid-resistant S. aureus, and methicillin-resistant S. epidermidis. WR12 and D-IK8 were able to eradicate persisters, MRSA in stationary growth phase, and showed significant clearance of intracellular MRSA in comparison to both vancomycin and linezolid. In vivo, topical WR12 and D-IK8 significantly reduced both the bacterial load and the levels of the pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in MRSA-infected skin lesions. Moreover, both peptides disrupted established in vitro biofilms of S. aureus and S. epidermidis significantly more so than traditional antimicrobials tested. Taken together, these results support the potential of WR12 and D-IK8 to be used as a topical antimicrobial agent for the treatment of staphylococcal skin infections.