Department of Studies in Zoology, Manasagangotri, University of Mysore, Mysore, India.
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
PLoS One. 2021 Sep 16;16(9):e0256664. doi: 10.1371/journal.pone.0256664. eCollection 2021.
The DNA polymorphisms found in clinical strains of Mycobacterium tuberculosis drive altered physiology, virulence, and pathogenesis in them. Although the lineages of these clinical strains can be traced back to common ancestor/s, there exists a plethora of difference between them, compared to those that have evolved in the laboratory. We identify a mutation present in ~80% of clinical strains, which maps in the HATPase domain of the sensor kinase MtrB and alters kinase and phosphatase activities, and affects its physiological role. The changes conferred by the mutation were probed by in-vitro biochemical assays which revealed changes in signaling properties of the sensor kinase. These changes also affect bacterial cell division rates, size and membrane properties. The study highlights the impact of DNA polymorphisms on the pathophysiology of clinical strains and provides insights into underlying mechanisms that drive signal transduction in pathogenic bacteria.
在结核分枝杆菌的临床分离株中发现的 DNA 多态性导致了它们生理机能、毒力和发病机制的改变。虽然这些临床分离株的谱系可以追溯到共同的祖先，但与在实验室中进化的菌株相比，它们之间存在着大量的差异。我们鉴定出存在于约 80%的临床分离株中的突变，该突变位于传感器激酶 MtrB 的 HATPase 结构域，改变了激酶和磷酸酶的活性，并影响了其生理功能。通过体外生化分析来探究突变赋予的变化，揭示了传感器激酶信号转导特性的变化。这些变化还影响了细菌的分裂速度、大小和膜特性。该研究强调了 DNA 多态性对临床分离株病理生理学的影响，并为驱动病原菌信号转导的潜在机制提供了新的见解。
