The antioxidant mimetic, MnTE-2-PyP, reduces intracellular growth of Mycobacterium abscessus.
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.
Oberley-Deegan
Rebecca E
RE
Department of Medicine, National Jewish Health, Denver, CO 80206, USA. oberleyr@njc.org
Lee
Young Min
YM
Morey
G Eli
GE
Cook
Danielle M
DM
Chan
Edward D
ED
Crapo
James D
JD
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000382:microbiology*; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009170:Nontuberculous Mycobacteria / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000975:Antioxidants; D016209:Interleukin-8; D008665:Metalloporphyrins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C520506:manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin; D013481:Superoxides; D009569:Nitric Oxide