c-di-AMP Accumulation Regulates Growth, Metabolism, and Immunogenicity of Mycobacterium smegmatis.
c-di-AMP Accumulation Regulates Growth, Metabolism, and Immunogenicity of Mycobacterium smegmatis.
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DOI：
10.3389/fmicb.2022.865045
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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作者：
环二聚腺苷单磷酸（c-di-AMP）是细菌普遍存在的第二信使，参与多种生理过程和宿主免疫反应。MSMEG_2630是耻垢分枝杆菌的c-二磷酸二酯酶（cnpB），与结核分枝杆菌Rv2837c同源。本研究构建了cnpb缺失（ΔcnpB）、-补充（ΔcnpB::C）和-过表达（ΔcnpB::O）的耻垢分枝杆菌菌株，研究了C -二- amp在调节分枝杆菌生理和免疫原性中的作用。本研究提供了更精确的证据，表明c-二- amp水平升高导致耻垢分枝杆菌菌落变小、细菌长度缩短、生长受损和钾转运蛋白抑制。本研究首次报道，升高的c-二- amp水平可通过调控相关基因表达，抑制褐皮分枝杆菌生物膜的形成，诱导卟啉积累，从而影响分枝杆菌的耐药和毒力。此外，cnpb缺失菌株c-di-AMP水平升高可诱导结核分枝杆菌感染后Th1免疫反应增强。此外，ΔcnpB组抗结核分枝杆菌静脉感染小鼠模型的病理变化和细菌负荷与野生型耻垢分枝杆菌组相当。我们的研究结果增强了对c-di-AMP在分枝杆菌中的生理作用的理解，耻垢分枝杆菌cnpb缺失菌株中c-di-AMP水平升高显示了抗结核疫苗的潜力。
Cyclic dimeric adenosine monophosphate (c-di-AMP) is a ubiquitous second messenger of bacteria involved in diverse physiological processes as well as host immune responses. MSMEG_2630 is a c-di-AMP phosphodiesterase (cnpB) of Mycobacterium smegmatis, which is homologous to Mycobacterium tuberculosis Rv2837c. In this study, cnpB-deleted (ΔcnpB), -complemented (ΔcnpB::C), and -overexpressed (ΔcnpB::O) strains of M. smegmatis were constructed to investigate the role of c-di-AMP in regulating mycobacterial physiology and immunogenicity. This study provides more precise evidence that elevated c-di-AMP level resulted in smaller colonies, shorter bacteria length, impaired growth, and inhibition of potassium transporter in M. smegmatis. This is the first study to report that elevated c-di-AMP level could inhibit biofilm formation and induce porphyrin accumulation in M. smegmatis by regulating associated gene expressions, which may have effects on drug resistance and virulence of mycobacterium. Moreover, the cnpB-deleted strain with an elevated c-di-AMP level could induce enhanced Th1 immune responses after M. tuberculosis infection. Further, the pathological changes and the bacteria burden in ΔcnpB group were comparable with the wild-type M. smegmatis group against M. tuberculosis venous infection in the mouse model. Our findings enhanced the understanding of the physiological role of c-di-AMP in mycobacterium, and M. smegmatis cnpB-deleted strain with elevated c-di-AMP level showed the potential for a vaccine against tuberculosis.
影响因子：
5.2
作者：
Li M;Gašparovič H;Weng X;Chen S;Korduláková J;Jessen-Trefzer C
通讯作者：
Jessen-Trefzer C