The antioxidant mimetic, MnTE-2-PyP, reduces intracellular growth of Mycobacterium abscessus

Am J Respir Cell Mol Biol. 2009 Aug;41(2):170-8. doi: 10.1165/rcmb.2008-0138OC. Epub 2008 Dec 18.

Abstract

Mycobacterium abscessus is a rapidly growing environmental mycobacterium that can cause severe skin, soft tissue, and lung infections. M. abscessus grows inside macrophages, and these cells release a vast number of proinflammatory cytokines in response to infections. The metalloporphyrin, MnTE-2-PyP, is a broad antioxidant that reduces inflammatory cell signaling. Macrophage-like THP-1 cells were infected with M. abscessus in the presence or absence of MnTE-2-PyP. MnTE-2-PyP significantly decreased, in a dose-dependent manner, the number of M. abscessus organisms recovered from infected THP-1 cells 4 and 8 days after infection. Furthermore, when combined with clarithromycin, MnTE-2-PyP additively reduced the number of cells associated with M. abscessus. A mechanism of bacterial growth inhibition by MnTE-2-PyP was then elucidated. It was found that MnTE-2-PyP promoted the survival of infected THP-1 cells and increased fusion of M. abscessus-containing phagosomes with lysosomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cell Line
  • Humans
  • Interleukin-8 / immunology
  • Lysosomes / metabolism
  • Macrophages / cytology
  • Macrophages / microbiology*
  • Metalloporphyrins / chemistry
  • Metalloporphyrins / pharmacology*
  • Microbial Sensitivity Tests
  • Monocytes / cytology
  • Monocytes / physiology
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nontuberculous Mycobacteria / drug effects*
  • Nontuberculous Mycobacteria / physiology
  • Phagocytosis
  • Phagosomes / metabolism
  • Superoxides / metabolism
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antioxidants
  • Interleukin-8
  • Metalloporphyrins
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin
  • Superoxides
  • Nitric Oxide