Xie Weile, Luo Dan, Soni Vijay, Wang Zhe
Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China; Collaborative Innovation Center of Agri-Seeds / School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Division of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medicine, New York, NY, United States.
Vaccine. 2025 Feb 27;48:126720. doi: 10.1016/j.vaccine.2025.126720. Epub 2025 Jan 13.
The Pro-Glu/Pro-Pro-Glu (PE/PPE) family proteins in mycobacteria plays a crucial role in pathogenesis and immune evasion. These proteins characterized by unique structures with conserved sequences. This study elucidated the specific immunological functions of MMAR_1296 from marine mycobacterium. Expressing MMAR_1296 in Mycobacterium smegmatis (M. smegmatis) led to significant alterations in bacterial morphology, as well as reduced survival of M. smegmatis under adverse in vitro conditions and within macrophages. Furthermore, transcriptome analysis of mouse macrophages indicated that natural immunity-related pathways were upregulated in the group infected with M. smegmatis recombinantly expressing MMAR_1296. Moreover, the mycobacterium Growth Inhibition Assays(MGIA)in mice demonstrated that M. smegmatis expressing MMAR_1296 exerted a significant inhibitory effect against Mycobacterium abscessus (M. abscessus) and Mycobacterium marinum (M. marinum) infections. Immunization challenge experiments in mice further confirmed its protective effects, showing a reduction in organ bacterial loads by 1 log value compared to the positive control group. These findings indicate that MMAR_1296 is a promising vaccine candidate for M. abscessus and M. marinum. Given that PE/PPE protein family is also a crucial component of Mycobacterium tuberculosis (M. tuberculosis) antigens, further exploration of sequence functions based on MMAR_1296 could reveal broader applications of PE/PPE proteins family for M. tuberculosis treatment. This study supported vaccine development targeting PE/PPE proteins in mycobacteria and paves the way for broader applications.
分枝杆菌中的脯氨酸 - 谷氨酸/脯氨酸 - 脯氨酸 - 谷氨酸（PE/PPE）家族蛋白在发病机制和免疫逃避中起着关键作用。这些蛋白具有独特的结构和保守序列。本研究阐明了海洋分枝杆菌中MMAR_1296的特定免疫功能。在耻垢分枝杆菌中表达MMAR_1296导致细菌形态发生显著变化，以及耻垢分枝杆菌在体外不利条件下和巨噬细胞内的存活率降低。此外，对小鼠巨噬细胞的转录组分析表明，在感染重组表达MMAR_1296的耻垢分枝杆菌的组中，天然免疫相关途径上调。此外，小鼠中的分枝杆菌生长抑制试验（MGIA）表明，表达MMAR_1296的耻垢分枝杆菌对脓肿分枝杆菌和海分枝杆菌感染具有显著的抑制作用。小鼠免疫挑战实验进一步证实了其保护作用，与阳性对照组相比，器官细菌载量降低了1个对数单位。这些发现表明，MMAR_1296是脓肿分枝杆菌和海分枝杆菌有前景的疫苗候选物。鉴于PE/PPE蛋白家族也是结核分枝杆菌抗原的关键组成部分，基于MMAR_1296进一步探索序列功能可能揭示PE/PPE蛋白家族在结核分枝杆菌治疗中的更广泛应用。本研究支持针对分枝杆菌中PE/PPE蛋白的疫苗开发，并为更广泛的应用铺平了道路。
