Synergistic effects of short peptides and antibiotics against bacterial and fungal strains,Journal of Peptide Science

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Synergistic effects of short peptides and antibiotics against bacterial and fungal strains
Journal of Peptide Science ( IF 1.8 ) Pub Date : 2022-08-05 , DOI: 10.1002/psc.3446
Lalita Sharma ₁ , Gopal Singh Bisht ₁

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There is a rising tide of concern about the antibiotic resistance issue. To reduce the possibility of antibiotic-resistant infections, a new generation of antimicrobials must be developed. Antimicrobial peptides are potential alternatives to antibiotics that can be used alone or together with conventional antibiotics to combat antimicrobial resistance. In this work, lead compounds LP-23, DP-23, SA4, and SPO from previously published studies were synthesized by solid-phase peptide synthesis and their antimicrobial evaluation was carried out against various bacterial and fungal strains. Peptide combinations with antibiotics were evaluated by using the checkerboard method and their minimal inhibitory concentration (MIC) in combination was calculated by using the fractional inhibitory concentration (FIC) index. Cytotoxicity evaluations of these peptides further confirmed their selectivity toward microbial cells. Based on the FIC values, LP-23, DP-23, and SPO demonstrated synergy in combination with gentamicin against a gentamicin-resistant clinical isolate of Escherichia coli. For Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium, seven combinations exhibited synergistic effects between peptide/peptoids and the tested antibiotics. Additionally, almost all the combinations of peptides/peptoids with amphotericin B and fluconazole also showed effective synergy against Aspergillus niger and Aspergillus flavus. The synergy found between LP-23, DP-23, SA4, and SPO with the selected antibiotics may have the potential to be used as a combination therapy against various microbial infections.

中文翻译：

短肽和抗生素对细菌和真菌菌株的协同作用

人们越来越关注抗生素耐药性问题。为了减少抗生素耐药性感染的可能性，必须开发新一代的抗菌剂。抗菌肽是抗生素的潜在替代品，可以单独使用或与传统抗生素一起使用以对抗抗菌素耐药性。在这项工作中，通过固相肽合成合成了先前发表的研究中的先导化合物 LP-23、DP-23、SA4 和 SPO，并针对各种细菌和真菌菌株进行了抗菌评估。使用棋盘法评估肽与抗生素的组合，并使用分数抑菌浓度 (FIC) 指数计算组合的最小抑菌浓度 (MIC)。这些肽的细胞毒性评估进一步证实了它们对微生物细胞的选择性。根据 FIC 值，LP-23、DP-23 和 SPO 显示与庆大霉素联合对抗庆大霉素耐药临床分离株的协同作用大肠杆菌。对于金黄色葡萄球菌、大肠杆菌和鼠伤寒沙门氏菌，七种组合在肽/拟肽和测试的抗生素之间表现出协同作用。此外，几乎所有肽/类肽与两性霉素 B 和氟康唑的组合也显示出对黑曲霉和黄曲霉的有效协同作用。LP-23、DP-23、SA4 和 SPO 与所选抗生素之间的协同作用可能有可能用作针对各种微生物感染的联合疗法。

更新日期：2022-08-05

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