Teng Tieshan, Liu Jiafa, Wei Hongping
Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Cell Physiol Biochem. 2015;35(2):452-66. doi: 10.1159/000369711. Epub 2015 Jan 15.
Mycobacterium tuberculosis is the major pathogen of tuberculosis (TB). With the growing problem of M. tuberculosis resistant to conventional antibiotics, especially multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the need for new TB drugs is now more prominent than ever. Among the promising candidates for anti-TB drugs, anti-mycobacterial peptides have a few advantages, such as low immunogenicity, selective affinity to prokaryotic negatively charged cell envelopes, and diverse modes of action. In this review, we summarize the recent progress in the anti-mycobacterial peptides, highlighting the sources, effectiveness and bactericidal mechanisms of these antimicrobial peptides. Most of the current anti-mycobacterial peptides are derived either from host immune cells, bacterial extraction, or mycobacteriophages. Besides trans-membrane pore formation, which is considered to be the common bactericidal mechanism, many of the anti-mycobacterial peptides have the second non-membrane targets within mycobacteria. Additionally, some antimicrobial peptides play critical roles in innate immunity. However, a few obstacles, such as short half-life in vivo and resistance to antimicrobial peptides, need overcoming before clinical applications. Nevertheless, the multiple functions of anti-mycobacterial peptides, especially direct killing of pathogens and immune-modulators in infectious and inflammatory conditions, indicate that they are promising candidates for future drug development.
结核分枝杆菌是结核病的主要病原体。随着结核分枝杆菌对传统抗生素耐药问题的日益严重，尤其是多重耐药结核病（MDR-TB）和广泛耐药结核病（XDR-TB），对新型抗结核药物的需求比以往任何时候都更加突出。在抗结核药物的有前景的候选药物中，抗分枝杆菌肽具有一些优势，如低免疫原性、对原核负电荷细胞膜的选择性亲和力以及多种作用方式。在本综述中，我们总结了抗分枝杆菌肽的最新进展，重点介绍了这些抗菌肽的来源、有效性和杀菌机制。目前大多数抗分枝杆菌肽要么来源于宿主免疫细胞、细菌提取物，要么来源于分枝杆菌噬菌体。除了被认为是常见杀菌机制的跨膜孔形成外，许多抗分枝杆菌肽在分枝杆菌内还有第二个非膜靶点。此外，一些抗菌肽在固有免疫中发挥关键作用。然而，在临床应用之前，还需要克服一些障碍，如体内半衰期短和对抗菌肽的耐药性。尽管如此，抗分枝杆菌肽的多种功能，尤其是在感染和炎症条件下直接杀灭病原体和免疫调节作用，表明它们是未来药物开发的有前景的候选药物。
