Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.
Graduate Studies, Manipal University, Manipal, India.
EMBO J. 2018 Jan 17;37(2):183-200. doi: 10.15252/embj.201796918. Epub 2017 Nov 23.
Host cell defense against an invading pathogen depends upon various multifactorial mechanisms, several of which remain undiscovered. Here, we report a novel defense mechanism against mycobacterial infection that utilizes the histone methyltransferase, SUV39H1. Normally, a part of the host chromatin, SUV39H1, was also found to be associated with the mycobacterial bacilli during infection. Its binding to bacilli was accompanied by trimethylation of the mycobacterial histone-like protein, HupB, which in turn reduced the cell adhesion capability of the bacilli. Importantly, SUV39H1-mediated methylation of HupB reduced the mycobacterial survival inside the host cell. This was also true in mice infection experiments. In addition, the ability of mycobacteria to form biofilms, a survival strategy of the bacteria dependent upon cell-cell adhesion, was dramatically reduced in the presence of SUV39H1. Thus, this novel defense mechanism against mycobacteria represents a surrogate function of the epigenetic modulator, SUV39H1, and operates by interfering with their cell-cell adhesion ability.
宿主细胞对入侵病原体的防御依赖于多种多因素机制，其中有几种仍未被发现。在这里，我们报告了一种针对分枝杆菌感染的新型防御机制，该机制利用了组蛋白甲基转移酶 SUV39H1。正常情况下，宿主染色质的一部分 SUV39H1 在感染过程中也与分枝杆菌杆菌有关。它与杆菌的结合伴随着分枝杆菌组蛋白样蛋白 HupB 的三甲基化，这反过来又降低了杆菌的细胞黏附能力。重要的是，SUV39H1 介导的 HupB 甲基化降低了分枝杆菌在宿主细胞内的存活能力。在小鼠感染实验中也是如此。此外，在存在 SUV39H1 的情况下，分枝杆菌形成生物膜的能力（一种依赖于细胞间黏附的细菌生存策略）显著降低。因此，这种针对分枝杆菌的新型防御机制代表了表观遗传调节剂 SUV39H1 的替代功能，通过干扰其细胞间黏附能力来发挥作用。
