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PLoS One ; 16(9): e0256664, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34529706

RESUMO

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.


Assuntos
Proteínas de Bactérias/genética , Mycobacterium tuberculosis , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genética , Tuberculose/microbiologia , Regulação Bacteriana da Expressão Gênica , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/patogenicidade , Polimorfismo de Nucleotídeo Único , Transdução de Sinais , Virulência
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