Wu Zhuhua, Liu Weilong, Tan Qiuchan, Chen Yuhui, Lai Xiaoyu, Hong Jianming, Liang Hongdi, Wu Huizhong, Liang Jing, Chen Xunxun
Key Laboratory of Translational Medicine of Guangdong, Center for Tuberculosis Control of Guangdong Province, Guangzhou, Guangdong, China.
Institute of Hepatology, Shenzhen Third People's Hospital, Shenzhen, Guangdong, China.
BMC Microbiol. 2025 Mar 8;25(1):124. doi: 10.1186/s12866-025-03826-7.
Pathways involving triacylglycerol (TAG) accumulation are thought to play a crucial regulatory role in bacterial growth and metabolism. Despite this understanding, little is known about the biological functions and regulatory mechanisms of small RNAs in Mycobacterium. Mycobacterium smegmatis (M. smegmatis), a type of Mycobacterium, serves as a model organism to investigate the molecular, physiological, and drug resistance features of M. tuberculosis.
In this study, we demonstrated that overexpression of B11 significantly affects bacterial growth and colony morphology, increases antibiotic sensitivity and sodium dodecyl sulfate (SDS) surface stress, decreases intracellular survival, and suppresses cytokine secretion in macrophages. Transcriptomic and lipidomic analyses revealed a metabolic downshift in the B11 overexpression strain, characterized by reduced levels of TAG. Furthermore, transmission electron microscopy showed that the B11 overexpression strain exhibited decreased cell wall thickness, leading to reduced biofilm formation and altered cell wall permeability. Additionally, we observed that B11 regulated certain target genes but did not directly bind to those proteins tested.
Taken together, these findings suggest that B11 plays important roles in Mycobacterium survival under antibiotic and SDS stresses, TAG accumulation, and contributes to antibiotic sensitivity through altered cell wall permeability.
涉及三酰甘油(TAG)积累的途径被认为在细菌生长和代谢中起关键调节作用。尽管有这种认识,但关于分枝杆菌中小RNA的生物学功能和调节机制知之甚少。耻垢分枝杆菌(M. smegmatis)作为一种分枝杆菌,是研究结核分枝杆菌分子、生理和耐药特性的模式生物。
在本研究中,我们证明B11的过表达显著影响细菌生长和菌落形态,增加抗生素敏感性和十二烷基硫酸钠(SDS)表面应激,降低细胞内存活率,并抑制巨噬细胞中细胞因子的分泌。转录组学和脂质组学分析揭示了B11过表达菌株的代谢下调,其特征是TAG水平降低。此外,透射电子显微镜显示B11过表达菌株的细胞壁厚度降低,导致生物膜形成减少和细胞壁通透性改变。此外,我们观察到B11调节某些靶基因,但不直接与测试的那些蛋白质结合。
综上所述,这些发现表明B11在分枝杆菌在抗生素和SDS应激下的存活、TAG积累中起重要作用,并通过改变细胞壁通透性导致抗生素敏感性。