Institute of Nano Science and Technology (INST), Habitat Centre, Phase-10, Sector-64, Mohali, Punjab-160062, India.
National JALMA Institute for Leprosy and Other Mycobacterial Diseases (ICMR), Tajganj, Agra-282001, India.
Curr Protein Pept Sci. 2022;23(10):643-656. doi: 10.2174/1389203723666220526161109.
Tuberculosis (TB) is a highly contagious infection with extensive mortality and morbidity. The rise of TB-superbugs (drug-resistant strains) with the increase of their resistance to conventional antibiotics has prompted a further search for new anti-mycobacterial agents. It is difficult to breach the barriers around TB bacteria, including mycolic cell wall, granuloma, biofilm and mucus, by conventional antibiotics in a short span of time. Hence, there is an essential need for molecules with an unconventional mode of action and structure that can efficiently break the barriers around mycobacterium. Antimicrobial peptides (AMP) are essential components of innate immunity having cationic and amphipathic characteristics. Lines of evidence show that AMPs have good myco-bactericidal and antibiofilm activity against normal as well as antibiotic-resistant TB bacteria. These peptides have shown direct killing of bacteria by membrane lysis and indirect killing by activation of innate immune response in host cells by interacting with the component of the bacterial membrane and intracellular targets through diverse mechanisms. Despite a good anti-mycobacterial activity, some undesirable characteristics are also associated with AMP, including hemolysis, cytotoxicity, susceptibility to proteolysis and poor pharmacokinetic profile, and hence only a few clinical studies have been conducted with these biomolecules. The design of new combinatorial therapies, including AMPs and particulate drug delivery systems, could be new potential alternatives to conventional antibiotics to fight MDR- and XDRTB. This review outlined the array of AMP roles in TB therapy, possible mechanisms of actions, activities, and current advances in pragmatic strategies to improve challenges accompanying the delivery of AMP for tuberculosis therapeutics.
结核病（TB）是一种具有高传染性和广泛致死率和发病率的感染。随着对传统抗生素耐药性的增加，结核超级细菌（耐药菌株）的出现促使人们进一步寻找新的抗分枝杆菌药物。传统抗生素很难在短时间内突破结核细菌周围的屏障，包括细胞壁、肉芽肿、生物膜和黏液。因此，我们迫切需要具有非传统作用模式和结构的分子来有效地突破分枝杆菌周围的屏障。抗菌肽（AMP）是先天免疫的重要组成部分，具有阳离子和两亲性特征。有证据表明，AMP 对正常和耐药结核细菌具有良好的杀菌和抗生物膜活性。这些肽通过与细菌膜的成分和通过多种机制与细胞内靶标相互作用，通过膜溶解直接杀死细菌，并通过激活宿主细胞中的先天免疫反应间接杀死细菌。尽管 AMP 具有良好的抗分枝杆菌活性，但也存在一些不理想的特性，包括溶血、细胞毒性、易被蛋白酶水解和较差的药代动力学特征，因此只有少数临床研究采用了这些生物分子。设计新的组合疗法，包括 AMP 和颗粒药物递送系统，可能是对抗 MDR 和 XDRTB 的传统抗生素的新潜在替代品。本文概述了 AMP 在结核病治疗中的作用、可能的作用机制、活性以及在改善 AMP 用于结核病治疗的递送所伴随的挑战方面的最新进展。
