Choi Munjeong, Cho Hye-Sun, Ahn Byeongyong, Prathap Somasundaram, Nagasundarapandian Soundrarajan, Park Chankyu
Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 05029, Korea.
Antibiotics (Basel). 2022 Jul 22;11(8):989. doi: 10.3390/antibiotics11080989.
Cathelicidins are potent antimicrobial peptides with broad spectrum antimicrobial activity in many vertebrates and an important component of the innate immune system. However, our understanding of the genetic variations and biological characteristics of bat cathelicidins is limited. In this study, we performed genome-level analysis of the antimicrobial peptide cathelicidins from seven bat species in the six families, listed 19 cathelicidin-like sequences, and showed that the number of functional cathelicidin genes differed among bat species. Based on the identified biochemical characteristics of bat cathelicidins, three cathelicidins, HA-CATH (from ), ML-CATH (from ), and PD-CATH (from ), with clear antimicrobial signatures were chemically synthesized and evaluated antimicrobial activity. HA-CATH showed narrow-spectrum antibacterial activity against a panel of 12 reference bacteria, comprising 6 Gram-negative and 6 Gram-positive strains. However, ML-CATH and PD-CATH showed potent antibacterial activity against a broad spectrum of Gram-negative and Gram-positive bacteria with minimum inhibitory concentration (MIC) of 1 and 3 μg/mL, respectively, against ML-CATH and PD-CATH also showed antifungal activities against and with MIC of 5 to 40 μg/mL, respectively, and 80% inhibition of the metabolism of hyphae at 80 μg/mL, while displaying minimal cytotoxicity to HaCaT cells. Taken together, although the spectrum and efficacy of bat cathelicidins were species-dependent, the antimicrobial activity of ML-CATH and PD-CATH was comparable to that of other highly active cathelicidins in vertebrates while having negligible cytotoxicity to mammalian cells. ML-CATH and PD-CATH can be exploited as promising candidates for the development of antimicrobial therapeutics.
猫抗菌肽是许多脊椎动物中具有广谱抗菌活性的强效抗菌肽，是先天免疫系统的重要组成部分。然而，我们对蝙蝠猫抗菌肽的基因变异和生物学特性的了解有限。在本研究中，我们对六个科的七种蝙蝠的抗菌肽猫抗菌肽进行了基因组水平分析，列出了19个类猫抗菌肽序列，并表明功能性猫抗菌肽基因的数量在不同蝙蝠物种中有所不同。基于已确定的蝙蝠猫抗菌肽的生化特性，化学合成了三种具有明确抗菌特征的猫抗菌肽，即HA-CATH（来自 ）、ML-CATH（来自 ）和PD-CATH（来自 ），并评估了它们的抗菌活性。HA-CATH对一组12种参考细菌表现出窄谱抗菌活性，包括6种革兰氏阴性菌和6种革兰氏阳性菌。然而，ML-CATH和PD-CATH对广谱革兰氏阴性菌和革兰氏阳性菌表现出强效抗菌活性，对 的最低抑菌浓度（MIC）分别为1和3 μg/mL，ML-CATH和PD-CATH对 和 也表现出抗真菌活性，MIC分别为5至40 μg/mL，在80 μg/mL时对 菌丝体的代谢有80%的抑制作用，同时对HaCaT细胞的细胞毒性最小。综上所述，尽管蝙蝠猫抗菌肽的谱和功效因物种而异，但ML-CATH和PD-CATH与脊椎动物中其他高活性猫抗菌肽的抗菌活性相当，而对哺乳动物细胞的细胞毒性可忽略不计。ML-CATH和PD-CATH可作为抗菌治疗药物开发的有前途的候选物。
