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源自牛乳铁蛋白和蟾蜍抗菌肽II的嵌合肽:对参考菌株和临床分离株的抗真菌活性

Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II: Antifungal Activity against Reference Strains and Clinical Isolates of spp.

作者信息

Aguirre-Guataqui Katherine, Márquez-Torres Mateo, Pineda-Castañeda Héctor Manuel, Vargas-Casanova Yerly, Ceballos-Garzon Andrés, Rivera-Monroy Zuly Jenny, García-Castañeda Javier Eduardo, Parra-Giraldo Claudia Marcela

机构信息

Human Proteomics and Mycosis Unit, Infectious Diseases Research Group, Department of Microbiology, Carrera 7 # 43-82 Lab 404 Building 52, Pontificia Universidad Javeriana, Bogotá 111321, Colombia.

Bacteriology Department, Universidad Colegio Mayor de Cundinamarca, Bogotá 111321, Colombia.

出版信息

Antibiotics (Basel). 2022 Nov 5;11(11):1561. doi: 10.3390/antibiotics11111561.

Abstract

Antimicrobial peptides (AMPs) are considered to be a valuable source for the identification and/or design of promising candidates for the development of antifungal treatments, since they have advantages such as lower tendency to induce resistance, ease of production, and high purity and safety. Bovine lactoferricin (LfcinB) and buforin II (BFII) are AMPs to which great antimicrobial potential has been attributed. The minimum motives with antimicrobial activity derived from LfcinB and BFII are RRWQWR and RLLR, respectively. Nine chimeras containing the minimum motives of both peptides were synthesized and their antifungal activity against fluconazole (FLC)-sensitive and resistant , , and strains was evaluated. The results showed that peptides C9: (RRWQWR)K-Ahx-RLLRRRLLR and C6: KKWQWK-Ahx-RLLRRLLR exhibited the greatest antifungal activity against two strains of , a FLC-sensitive reference strain and a FLC-resistant clinical isolate; no medically significant results were observed with the other chimeras evaluated (MIC ~200 µg/mL). The chimera C6 was also active against sensitive and resistant strains of and . The combination of branched polyvalent chimeras together with FLC showed a synergistic effect against In addition to exhibiting antifungal activity against reference strains and clinical isolates of spp., they also showed antibacterial activity against both Gram-positive and Gram-negative bacteria, suggesting that these chimeras exhibit a broad antimicrobial spectrum and can be considered to be promising molecules for therapeutic applications.

摘要

抗菌肽(AMPs)被认为是鉴定和/或设计抗真菌治疗有前景候选物的宝贵来源,因为它们具有诸如诱导耐药性的倾向较低、易于生产以及高纯度和安全性等优点。牛乳铁蛋白肽(LfcinB)和蟾蜍抗菌肽II(BFII)是具有巨大抗菌潜力的抗菌肽。分别源自LfcinB和BFII的具有抗菌活性的最小基序是RRWQWR和RLLR。合成了九种包含这两种肽最小基序的嵌合体,并评估了它们对氟康唑(FLC)敏感和耐药的白色念珠菌、热带念珠菌和近平滑念珠菌菌株的抗真菌活性。结果表明,肽C9:(RRWQWR)K-Ahx-RLLRRRLLR和C6:KKWQWK-Ahx-RLLRRLLR对两株白色念珠菌(一株FLC敏感参考菌株和一株FLC耐药临床分离株)表现出最大的抗真菌活性;对评估的其他嵌合体未观察到具有医学意义的结果(MIC~200µg/mL)。嵌合体C6对热带念珠菌和近平滑念珠菌的敏感和耐药菌株也有活性。分支多价嵌合体与FLC联合使用对白色念珠菌显示出协同作用。除了对白色念珠菌属的参考菌株和临床分离株表现出抗真菌活性外,它们还对革兰氏阳性和革兰氏阴性细菌均表现出抗菌活性,这表明这些嵌合体具有广泛的抗菌谱,可被认为是有前景的治疗应用分子。

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