Vieira Ana Paula Gonçalves Coelho, de Souza Amanda Neves, Lima William Gustavo, Brito Julio Cesar Moreira, Simião Daniela Carolina, Gonçalves Lucas Vinícius Ribeiro, Cordeiro Lídia Pereira Barbosa, de Oliveira Scoaris Denise, Fernandes Simone Odília Antunes, Resende Jarbas Magalhães, Bechinger Burkhard, Verly Rodrigo Moreira, de Lima Maria Elena
Faculdade de Saúde Santa Casa de Belo Horizonte, Programa de Pós-Graduação Stricto Sensu em Medicina e Biomedicina, Belo Horizonte 30150-240, Brazil.
Departamento de Química, FACET, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM)-Campus JK, Diamantina 39100-000, Brazil.
Antibiotics (Basel). 2024 Mar 8;13(3):248. doi: 10.3390/antibiotics13030248.
The urgent global health challenge posed by methicillin-resistant (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.
耐甲氧西林金黄色葡萄球菌（MRSA）感染带来的紧迫全球健康挑战需要有效的解决方案。抗菌肽（AMPs）是新型抗菌剂研究的有前景的工具，基于蜘蛛毒液的短合成肽LyeTx I mn∆K就是一个很好的代表。本研究聚焦于分析LyeTx I mn∆K的抗菌活性，包括最小抑菌浓度和杀菌浓度、协同作用和再敏化试验、裂解活性、对生物膜的影响以及MRSA中的细菌死亡曲线。此外，通过等温滴定量热法、动态光散射、钙黄绿素释放对其进行了表征，最后在小鼠伤口模型中评估了其疗效。该肽对MRSA的浮游细胞（MIC为8 - 16 µM）和生物膜（抑制率>30%）具有显著疗效，在快速杀菌作用和抗生物膜效果方面优于万古霉素。其作用机制涉及显著的膜损伤。与细菌模型膜的相互作用，包括那些具有赖氨酰磷脂酰甘油（LysylPOPG）修饰的膜，突出了该化合物的多功能性和选择性。此外，该肽能够使耐药菌对传统抗生素敏感，显示出联合治疗的潜力。此外，本研究使用体内模型表明，含有该肽的配方凝胶在治疗小鼠MRSA诱导的伤口方面优于万古霉素。总之，这些结果突出了LyeTx I mnΔK作为开发针对浅表MRSA感染的有效治疗策略的有前景的原型。
