Phosphorylation of KasB Regulates Virulence and Acid-Fastness in
Acid-fast staining has been used since 1882 as the hallmark diagnostic test for detecting Mycobacterium tuberculosis, the causative agent of tuberculosis. It has been attributed to the presence of a waxy cell envelope, and primarily to its key components, mycolic acids. Here, we report a new mechanism of regulation in which phosphorylation of KasB, involved in the completion of full-length mycolic acids, leads to shortened mycolic acids and loss of acid-fast staining. Moreover, a M. tuberculosis mutant strain mimicking constitutive phosphorylation of KasB is severely attenuated for growth in both immunocompetent and immunosuppressed mice and fails to cause mortality and pathophysiological symptoms. These results emphasize the critical role of kinase-dependent phosphorylation in the pathogenesis of M. tuberculosis by controlling the mycolic acid chain length. Our study demonstrates the importance of a regulatory mechanism governing acid-fastness and virulence of M. tuberculosis.
Vyšlo v časopise:
Phosphorylation of KasB Regulates Virulence and Acid-Fastness in. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004115
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004115
Souhrn
Acid-fast staining has been used since 1882 as the hallmark diagnostic test for detecting Mycobacterium tuberculosis, the causative agent of tuberculosis. It has been attributed to the presence of a waxy cell envelope, and primarily to its key components, mycolic acids. Here, we report a new mechanism of regulation in which phosphorylation of KasB, involved in the completion of full-length mycolic acids, leads to shortened mycolic acids and loss of acid-fast staining. Moreover, a M. tuberculosis mutant strain mimicking constitutive phosphorylation of KasB is severely attenuated for growth in both immunocompetent and immunosuppressed mice and fails to cause mortality and pathophysiological symptoms. These results emphasize the critical role of kinase-dependent phosphorylation in the pathogenesis of M. tuberculosis by controlling the mycolic acid chain length. Our study demonstrates the importance of a regulatory mechanism governing acid-fastness and virulence of M. tuberculosis.
Zdroje
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