Protein kinase E of Mycobacterium tuberculosis has a role in the nitric oxide stress response and apoptosis in a human macrophage model of infection

Deepak Jayakumar, William R. Jacobs, Sujatha Narayanan

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Mycobacterium tuberculosis, an intracellular pathogen, inhibits macrophage apoptosis to support survival and replication inside the host cell. We provide evidence that the functional serine/threonine kinase, PknE, is important for survival of M.tuberculosis that enhances macrophage viability by inhibiting apoptosis. A promoter of PknE identified in this study was shown to respond to nitric oxide stress. Deletion of pknE in virulent M. tuberculosis, H37Rv, resulted in a strain that has increased resistance to nitric oxide donors and increased sensitivity to reducing agents. The deletion mutant created by specialized transduction induced enhanced apoptosis while inhibiting necrosis. The pknE mutant also modifies the innate immune response as shown by the marked decline in the pro-inflammatory cytokines in a macrophage model of infection. These findings suggest a novel mechanism, by which PknE senses nitric oxide stress and prevents apoptosis by interfering with host signalling pathways.

Original languageEnglish (US)
Pages (from-to)365-374
Number of pages10
JournalCellular Microbiology
Volume10
Issue number2
DOIs
StatePublished - Feb 1 2008

Fingerprint

Mycobacterium tuberculosis
Protein Kinases
Nitric Oxide
Macrophages
Apoptosis
Infection
Survival
Nitric Oxide Donors
Protein-Serine-Threonine Kinases
Reducing Agents
Innate Immunity
Tuberculosis
Necrosis
Cytokines

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Cite this

Protein kinase E of Mycobacterium tuberculosis has a role in the nitric oxide stress response and apoptosis in a human macrophage model of infection. / Jayakumar, Deepak; Jacobs, William R.; Narayanan, Sujatha.

In: Cellular Microbiology, Vol. 10, No. 2, 01.02.2008, p. 365-374.

Research output: Contribution to journalArticle

@article{597c46030052419fb96eb986e4bc21a9,
title = "Protein kinase E of Mycobacterium tuberculosis has a role in the nitric oxide stress response and apoptosis in a human macrophage model of infection",
abstract = "Mycobacterium tuberculosis, an intracellular pathogen, inhibits macrophage apoptosis to support survival and replication inside the host cell. We provide evidence that the functional serine/threonine kinase, PknE, is important for survival of M.tuberculosis that enhances macrophage viability by inhibiting apoptosis. A promoter of PknE identified in this study was shown to respond to nitric oxide stress. Deletion of pknE in virulent M. tuberculosis, H37Rv, resulted in a strain that has increased resistance to nitric oxide donors and increased sensitivity to reducing agents. The deletion mutant created by specialized transduction induced enhanced apoptosis while inhibiting necrosis. The pknE mutant also modifies the innate immune response as shown by the marked decline in the pro-inflammatory cytokines in a macrophage model of infection. These findings suggest a novel mechanism, by which PknE senses nitric oxide stress and prevents apoptosis by interfering with host signalling pathways.",
author = "Deepak Jayakumar and Jacobs, {William R.} and Sujatha Narayanan",
year = "2008",
month = "2",
day = "1",
doi = "10.1111/j.1462-5822.2007.01049.x",
language = "English (US)",
volume = "10",
pages = "365--374",
journal = "Cellular Microbiology",
issn = "1462-5814",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Protein kinase E of Mycobacterium tuberculosis has a role in the nitric oxide stress response and apoptosis in a human macrophage model of infection

AU - Jayakumar, Deepak

AU - Jacobs, William R.

AU - Narayanan, Sujatha

PY - 2008/2/1

Y1 - 2008/2/1

N2 - Mycobacterium tuberculosis, an intracellular pathogen, inhibits macrophage apoptosis to support survival and replication inside the host cell. We provide evidence that the functional serine/threonine kinase, PknE, is important for survival of M.tuberculosis that enhances macrophage viability by inhibiting apoptosis. A promoter of PknE identified in this study was shown to respond to nitric oxide stress. Deletion of pknE in virulent M. tuberculosis, H37Rv, resulted in a strain that has increased resistance to nitric oxide donors and increased sensitivity to reducing agents. The deletion mutant created by specialized transduction induced enhanced apoptosis while inhibiting necrosis. The pknE mutant also modifies the innate immune response as shown by the marked decline in the pro-inflammatory cytokines in a macrophage model of infection. These findings suggest a novel mechanism, by which PknE senses nitric oxide stress and prevents apoptosis by interfering with host signalling pathways.

AB - Mycobacterium tuberculosis, an intracellular pathogen, inhibits macrophage apoptosis to support survival and replication inside the host cell. We provide evidence that the functional serine/threonine kinase, PknE, is important for survival of M.tuberculosis that enhances macrophage viability by inhibiting apoptosis. A promoter of PknE identified in this study was shown to respond to nitric oxide stress. Deletion of pknE in virulent M. tuberculosis, H37Rv, resulted in a strain that has increased resistance to nitric oxide donors and increased sensitivity to reducing agents. The deletion mutant created by specialized transduction induced enhanced apoptosis while inhibiting necrosis. The pknE mutant also modifies the innate immune response as shown by the marked decline in the pro-inflammatory cytokines in a macrophage model of infection. These findings suggest a novel mechanism, by which PknE senses nitric oxide stress and prevents apoptosis by interfering with host signalling pathways.

UR - http://www.scopus.com/inward/record.url?scp=38049097940&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38049097940&partnerID=8YFLogxK

U2 - 10.1111/j.1462-5822.2007.01049.x

DO - 10.1111/j.1462-5822.2007.01049.x

M3 - Article

C2 - 17892498

AN - SCOPUS:38049097940

VL - 10

SP - 365

EP - 374

JO - Cellular Microbiology

JF - Cellular Microbiology

SN - 1462-5814

IS - 2

ER -