Potential role for ESAT6 in dissemination of M. tuberculosis via human lung epithelial cells

Arvind G. Kinhikar, Indu Verma, Dinesh Chandra, Krishna K. Singh, Karin Weldingh, Peter Andersen, Tsungda Hsu, William R. Jacobs, Suman Laal

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

ESAT6 has recently been demonstrated to cause haemolysis and macrophage lysis. Our studies demonstrate that ESAT6 causes cytolysis of type 1 and type 2 pneumocytes. Both types of pneumocytes express membrane laminin, and ESAT6 exhibits dose-dependent binding to both cell types and to purified human laminin. While minimal ESAT6 was detected on the surface of Mycobacterium tuberculosis grown in vitro, exogenously provided ESAT6 specifically associated with the bacterial cell surface, and the bacterium-associated ESAT6 retained its cytolytic ability. esat6 transcripts were upregulated ∼4- to ∼13-fold in bacteria replicating in type 1 cells, and ∼3- to ∼5 fold in type 2 cells. In vivo, laminin is primarily concentrated at the basolateral surface of pneumocytes where they rest on the basement membrane, which is composed primarily of laminin and collagen. The upregulation of esat6 transcripts in bacteria replicating in pneumocytes, the specific association of ESAT6 with the bacterial surface, the binding of ESAT6 to laminin and the lysis of pneumocytes by free and bacterium-associated ESAT6 together suggest a scenario wherein Mycobacterium tuberculosis replicating in pneumocytes may utilize surface ESAT6 to anchor onto the basolateral laminin-expressing surface of the pneumocytes, and damage the cells and the basement membrane to directly disseminate through the alveolar wall.

Original languageEnglish (US)
Pages (from-to)92-106
Number of pages15
JournalMolecular Microbiology
Volume75
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Fingerprint

Alveolar Epithelial Cells
Tuberculosis
Laminin
Epithelial Cells
Lung
Bacteria
Mycobacterium tuberculosis
Basement Membrane
Hemolysis
Up-Regulation
Collagen
Macrophages
Cell Membrane
Membranes

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Kinhikar, A. G., Verma, I., Chandra, D., Singh, K. K., Weldingh, K., Andersen, P., ... Laal, S. (2010). Potential role for ESAT6 in dissemination of M. tuberculosis via human lung epithelial cells. Molecular Microbiology, 75(1), 92-106. https://doi.org/10.1111/j.1365-2958.2009.06959.x

Potential role for ESAT6 in dissemination of M. tuberculosis via human lung epithelial cells. / Kinhikar, Arvind G.; Verma, Indu; Chandra, Dinesh; Singh, Krishna K.; Weldingh, Karin; Andersen, Peter; Hsu, Tsungda; Jacobs, William R.; Laal, Suman.

In: Molecular Microbiology, Vol. 75, No. 1, 01.2010, p. 92-106.

Research output: Contribution to journalArticle

Kinhikar, AG, Verma, I, Chandra, D, Singh, KK, Weldingh, K, Andersen, P, Hsu, T, Jacobs, WR & Laal, S 2010, 'Potential role for ESAT6 in dissemination of M. tuberculosis via human lung epithelial cells', Molecular Microbiology, vol. 75, no. 1, pp. 92-106. https://doi.org/10.1111/j.1365-2958.2009.06959.x
Kinhikar, Arvind G. ; Verma, Indu ; Chandra, Dinesh ; Singh, Krishna K. ; Weldingh, Karin ; Andersen, Peter ; Hsu, Tsungda ; Jacobs, William R. ; Laal, Suman. / Potential role for ESAT6 in dissemination of M. tuberculosis via human lung epithelial cells. In: Molecular Microbiology. 2010 ; Vol. 75, No. 1. pp. 92-106.
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