Koleske Benjamin, Schill Courtney, Rajagopalan Saranathan, Shee Somnath, Martinez-Martinez Yazmin B, Gupta Manish, Shen Jessica, Jacobs William R, Bishai William R
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Sci Adv. 2025 Jul 4;11(27):eadw5194. doi: 10.1126/sciadv.adw5194. Epub 2025 Jul 2.
() is remarkable for its immense global disease burden and low mutation rate. Despite strong selective pressure, shows frequent deletions at the - locus, most notably in hypervirulent L2 Beijing strains. Here, we show that loss of the - locus causes increased stress response gene expression and increased triglyceride levels. In addition, we demonstrate that reintroduction of into the L2 strain HN878 suppresses the baseline elevation of these transcripts, while overexpression of increases the localization of PE_PGRS proteins and lipoproteins to the outer mycomembrane. Mouse infection confirmed the hypervirulence of the - deletion strain and conversely showed that overexpression attenuates . Our results indicate that loss of - is sufficient to drive an adaptive transcriptional response seen in L2 strains that likely contributes to the hypervirulence of this lineage.
（）因其巨大的全球疾病负担和低突变率而引人注目。尽管存在强大的选择压力，但在 - 位点仍频繁出现缺失，最显著的是在高毒力L2北京菌株中。在这里，我们表明 - 位点的缺失会导致应激反应基因表达增加和甘油三酯水平升高。此外，我们证明将 重新引入L2菌株HN878可抑制这些转录本的基线升高，而 的过表达会增加PE_PGRS蛋白和脂蛋白在外膜的定位。小鼠感染证实了 - 缺失菌株的高毒力，相反表明 过表达会减弱 。我们的结果表明， - 的缺失足以驱动在L2菌株中观察到的适应性转录反应，这可能有助于该谱系的高毒力。
