Efficacy of Cathelicidin-Mimetic Antimicrobial Peptoids against Staphylococcus aureus.
Efficacy of Cathelicidin-Mimetic Antimicrobial Peptoids against Staphylococcus aureus.
复制标题
DOI：
10.1128/spectrum.00534-22
复制
发表时间：
2022-06-29
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
金黄色葡萄球菌是与伤口感染相关的最常见病原体之一。目前的护理标准使用消毒和引流的组合，然后使用常规抗生素，如甲氧西林。甲氧西林和万古霉素耐药性使这些治疗无效，经常导致感染复发。本研究探讨了使用抗微生物类肽（序列特异性聚-N-取代甘氨酸），旨在模拟天然存在的阳离子，两亲性宿主防御肽，作为替代传统抗生素。这些类肽还显示出对甲氧西林敏感的S.金黄色葡萄球菌（MSSA）和耐甲氧西林的S.金黄色葡萄球菌（MRSA）在低微摩尔浓度，而没有明显的细胞毒性副作用，在体内。此外，这些新型类肽显示出针对MSSA和MRSA的生物膜形成和脱离的优异功效。相比之下，常规抗生素无法分离或防止生物膜的形成。一种阳离子12聚体Peptoid 1显示出巨大的前景，因为它可以在低至1.6 μM的浓度下防止生物膜的形成和分离。使用生物发光的S。金黄色葡萄球菌鼠切口伤口模型显示，在8天内类肽处理的小鼠中感染被清除，传达了这些类肽相对于常规抗生素的另一个优点。这些结果提供了明确的证据，表明抗微生物类肽具有治疗沙门氏菌的潜力。金黄色葡萄球菌伤口感染重要性金黄色葡萄球菌耐药性是一个长期存在的问题，对卫生保健系统有很大的影响。感染耐药的S.金黄色葡萄球菌可引起严重的副作用并可导致死亡。这些抗微生物类肽可有效杀灭生物膜和游离细菌，通常在不到30分钟内完成。因此，这些抗微生物剂有可能减轻葡萄球菌感染对医疗保健系统的负担，并为感染患者带来更好的结果。
Staphylococcus aureus is one of the most common pathogens associated with infection in wounds. The current standard of care uses a combination of disinfection and drainage followed by conventional antibiotics such as methicillin. Methicillin and vancomycin resistance has rendered these treatments ineffective, often causing the reemergence of infection. This study examines the use of antimicrobial peptoids (sequence-specific poly-N-substituted glycines) designed to mimic naturally occurring cationic, amphipathic host defense peptides, as an alternative to conventional antibiotics. These peptoids also show efficient and fast (<30 min) killing of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) at low micromolar concentrations without having apparent cytotoxic side effects in vivo. Additionally, these novel peptoids show excellent efficacy against biofilm formation and detachment for both MSSA and MRSA. In comparison, conventional antibiotics were unable to detach or prevent formation of biofilms. One cationic 12mer, Peptoid 1, shows great promise, as it could prevent formation of and detach biofilms at concentrations as low as 1.6 μM. The use of a bioluminescent S. aureus murine incision wound model demonstrated clearance of infection in peptoid-treated mice within 8 days, conveying another advantage these peptoids have over conventional antibiotics. These results provide clear evidence of the potential for antimicrobial peptoids for the treatment of S. aureus wound infections. IMPORTANCE Staphylococcus aureus resistance is a consistent problem with a large impact on the health care system. Infections with resistant S. aureus can cause serious adverse effects and can result in death. These antimicrobial peptoids show efficient killing of bacteria both as a biofilm and as free bacteria, often doing so in less than 30 min. As such, these antimicrobials have the potential to alleviate the burden that Staphylococcus infections have on the health care system and cause better outcomes for infected patients.
登录
查看更多内容
影响因子：
3.6
作者：
Contag, CH;Contag, PR;Benaron, DA
通讯作者：
Benaron, DA
影响因子：
4.6
作者：
Chongsiriwatana NP;Lin JS;Kapoor R;Wetzler M;Rea JAC;Didwania MK;Contag CH;Barron AE
通讯作者：
Barron AE
影响因子：
158.5
作者：
LECLERCQ, R;DERLOT, E;COURVALIN, P
通讯作者：
COURVALIN, P
影响因子：
3.7
作者：
Huang W;Seo J;Willingham SB;Czyzewski AM;Gonzalgo ML;Weissman IL;Barron AE
通讯作者：
Barron AE
影响因子：
4.9
作者：
Chongsiriwatana, Nathaniel P.;Wetzler, Modi;Barron, Annelise E.
通讯作者：
Barron, Annelise E.