Mycobacterium tuberculosis TlyA protein negatively regulates T helper (Th) 1 and Th17 differentiation and promotes tuberculosis pathogenesis

Md Aejazur Rahman, Parveen Sobia, Ved Prakash Dwivedi, Aakansha Bhawsar, Dhiraj Kumar Singh, Pawan Sharma, Prashini Moodley, Luc Van Kaer, William Ramses Bishai, Gobardhan Das

Research output: Contribution to journalArticle

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M. tuberculosis have been identified, its pathogenesis remains incompletely understood. TlyA is a virulence factor in several bacterial infections and is evolutionarily conserved in many Gram-positive bacteria, but its function in M. tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA significantly contributes to the pathogenesis of M. tuberculosis. We show that a TlyA mutant M. tuberculosis strain induces increased IL-12 and reduced IL-1β and IL-10 cytokine responses, which sharply contrasts with the immune responses induced by wild typeM. tuberculosis. Furthermore, compared with wild type M. tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to autophagy in macrophages. Consequently, animals infected with the TlyA mutant M. tuberculosis organisms exhibited increased host-protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host evasion factor, thereby contributing to its virulence.

Original languageEnglish (US)
Pages (from-to)14407-14417
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number23
DOIs
StatePublished - Jun 5 2015

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Virulence Factors
Mycobacterium tuberculosis
Bacteria
Animals
Tuberculosis
Macrophages
Pathogens
Interleukin-12
Interleukin-1
Interleukin-10
Cytokines
Mycobacterium tuberculosis TlyA protein
Autophagy
Gram-Positive Bacteria
Bacterial Infections
Virulence
Cause of Death

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Mycobacterium tuberculosis TlyA protein negatively regulates T helper (Th) 1 and Th17 differentiation and promotes tuberculosis pathogenesis. / Rahman, Md Aejazur; Sobia, Parveen; Dwivedi, Ved Prakash; Bhawsar, Aakansha; Singh, Dhiraj Kumar; Sharma, Pawan; Moodley, Prashini; Kaer, Luc Van; Bishai, William Ramses; Das, Gobardhan.

In: Journal of Biological Chemistry, Vol. 290, No. 23, 05.06.2015, p. 14407-14417.

Research output: Contribution to journalArticle

Rahman, Md Aejazur ; Sobia, Parveen ; Dwivedi, Ved Prakash ; Bhawsar, Aakansha ; Singh, Dhiraj Kumar ; Sharma, Pawan ; Moodley, Prashini ; Kaer, Luc Van ; Bishai, William Ramses ; Das, Gobardhan. / Mycobacterium tuberculosis TlyA protein negatively regulates T helper (Th) 1 and Th17 differentiation and promotes tuberculosis pathogenesis. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 23. pp. 14407-14417.
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