The Antioxidant Mimetic, MnTE-2-PyP, Reduces Intracellular Growth of Mycobacterium abscessus

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.

Innate response of human endothelial cells infected with mycobacteria

“…Data are expressed as means ± SD from three different experiments. Only MTB infection induced a significant overexpression of hBD-1 gene *p < 0.05; **p < 0.01; ***p < 0.001. by the endothelial cells, and in spite of this, bacterial replication could not be controlled by the HUVECs; similar to this observation, a previous report, demonstrated that NO did not have any effect on MAB control in a macrophage in vitro model (Oberley-Deegan et al 2009). A possible explanation for this phenomenon is that MAB, compared to other mycobacteria (like M. tuberculosis), could be especially resistant to NO, but this is something that has to be studied.…”

Antioxidants: Friend or foe for tuberculosis patients

“…Such observations are also confirmed with other antioxidants like manganese (II) mesotetrakis-(N-methylpyridinium-2-yl) porphyrin [27]. Further, glutathione is known to modulate the T cell mediated immune response in a manner that reduces the intracellular stability of the tuberculosis bacterium [28].…”

The distinct fate of smooth and roughMycobacterium abscessusvariants inside macrophages

“…In this context, Oberley-Deegan et al . proposed that M. abscessus could interfere with phagosome processing into phagolysosomes through the manipulation of host signal transduction pathways [27,54]. …”