Turapov Obolbek, Loraine Jessica, Jenkins Christopher H, Barthe Philippe, McFeely Daniel, Forti Francesca, Ghisotti Daniela, Hesek Dusan, Lee Mijoon, Bottrill Andrew R, Vollmer Waldemar, Mobashery Shahriar, Cohen-Gonsaud Martin, Mukamolova Galina V
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UK.
Centre de Biochimie Structurale, CNRS UMR 5048, 29, rue de Navacelles, Montpellier 34090, France INSERM U1054, Université Montpellier I et II, Montpellier, France.
Open Biol. 2015 Jul;5(7):150025. doi: 10.1098/rsob.150025.
PknB is an essential serine/threonine protein kinase required for mycobacterial cell division and cell-wall biosynthesis. Here we demonstrate that overexpression of the external PknB_PASTA domain in mycobacteria results in delayed regrowth, accumulation of elongated bacteria and increased sensitivity to β-lactam antibiotics. These changes are accompanied by altered production of certain enzymes involved in cell-wall biosynthesis as revealed by proteomics studies. The growth inhibition caused by overexpression of the PknB_PASTA domain is completely abolished by enhanced concentration of magnesium ions, but not muropeptides. Finally, we show that the addition of recombinant PASTA domain could prevent regrowth of Mycobacterium tuberculosis, and therefore offers an alternative opportunity to control replication of this pathogen. These results suggest that the PknB_PASTA domain is involved in regulation of peptidoglycan biosynthesis and maintenance of cell-wall architecture.
PknB是一种分枝杆菌细胞分裂和细胞壁生物合成所必需的丝氨酸/苏氨酸蛋白激酶。在此，我们证明分枝杆菌中外源PknB_PASTA结构域的过表达导致再生延迟、细长细菌积累以及对β-内酰胺抗生素敏感性增加。蛋白质组学研究表明，这些变化伴随着细胞壁生物合成中某些酶的产生改变。PknB_PASTA结构域过表达引起的生长抑制可通过提高镁离子浓度完全消除，但不能通过胞壁肽消除。最后，我们表明添加重组PASTA结构域可以阻止结核分枝杆菌的再生，因此为控制这种病原体的复制提供了另一种机会。这些结果表明，PknB_PASTA结构域参与肽聚糖生物合成的调控和细胞壁结构的维持。
