Avignon Université, INRAE, UMR SQPOV, F-84914, Avignon, France.
Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, 30200, Bagnols-sur-Cèze, France.
Biochimie. 2024 Sep;224:51-61. doi: 10.1016/j.biochi.2024.02.008. Epub 2024 Feb 27.
A structural homolog of the mammalian TSPO has been identified in the human pathogen Bacillus cereus. BcTSPO, in its recombinant form, has previously been shown to bind and degrade porphyrins. In this study, we generated a ΔtspO mutant strain in B. cereus ATCC 14579 and assessed the impact of the absence of BcTSPO on cellular proteomics and physiological characteristics. The proteomic analysis revealed correlations between the lack of BcTSPO and the observed growth defects, increased oxygen consumption, ATP deficiency, heightened tryptophan catabolism, reduced motility, and impaired biofilm formation in the ΔtspO mutant strain. Our results also suggested that BcTSPO plays a crucial role in regulating intracellular levels of metabolites from the coproporphyrin-dependent branch of the heme biosynthetic pathway. This regulation potentially underlies alterations in the metabolic landscape, emphasizing the pivotal role of BcTSPO in B. cereus aerobic metabolism. Notably, our study unveils, for the first time, the involvement of TSPO in tryptophan metabolism. These findings underscore the multifaceted role of TSPO, not only in metabolic pathways but also potentially in the microorganism's virulence mechanisms.
已经在人类病原体蜡状芽孢杆菌中鉴定出哺乳动物 TSPO 的结构同源物。重组形式的 BcTSPO 先前已被证明能结合和降解卟啉。在这项研究中，我们在蜡状芽孢杆菌 ATCC 14579 中生成了一个 ΔtspO 突变株，并评估了 BcTSPO 缺失对细胞蛋白质组学和生理特性的影响。蛋白质组学分析表明，BcTSPO 的缺失与观察到的生长缺陷、耗氧量增加、ATP 缺乏、色氨酸分解代谢增加、运动性降低以及生物膜形成受损之间存在相关性。我们的结果还表明，BcTSPO 在调节血红素生物合成途径中依赖粪卟啉的分支的细胞内代谢物水平方面发挥着关键作用。这种调节可能导致代谢景观的改变，强调了 BcTSPO 在蜡状芽孢杆菌需氧代谢中的关键作用。值得注意的是，我们的研究首次揭示了 TSPO 参与色氨酸代谢。这些发现强调了 TSPO 的多方面作用，不仅在代谢途径中，而且可能在微生物的毒力机制中。
