title: An oxidative environment promotes growth of Mycobacterium abscessus.
abstract: Mycobacterium abscessus infections, particularly those causing chronic lung diseases, are becoming more prevalent worldwide. M. abscessus infections are difficult to treat because of antibiotic resistance. Thus, new treatment options are urgently needed. M. abscessus is an intracellular pathogen that primarily infects macrophages and fibroblasts. Because this bacterium has only recently been identified as a separate species, very little is known about M. abscessus-host interactions and how M. abscessus growth is regulated. Oxidative stress has long been shown to inhibit the growth of bacterial organisms. However, some intracellular bacteria, such as Mycobacterium tuberculosis, grow well in oxidizing environments. In this study, we show that M. abscessus infection causes the host cell environment to become more oxidizing. Furthermore, we show that a more oxidizing environment leads to enhanced growth of M. abscessus inside macrophages. In the presence of antioxidants, MnTE-2-PyP (chemical name: manganese(II) meso-tetrakis-(N-methylpyridinium-2-yl) porphyrin) or N-acetyl-l-cysteine, M. abscessus growth is inhibited. These results lead us to postulate that antioxidants may aid in the treatment of M. abscessus infections.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO 80206, USA. oberleyr@njc.org
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Oberley-Deegan
authors.forename: Brittany W
authors.initials: BW
authors.lastname: Rebits
authors.forename: Michael R
authors.initials: MR
authors.lastname: Weaver
authors.forename: Angela K
authors.initials: AK
authors.lastname: Tollefson
authors.forename: Xiyuan
authors.initials: X
authors.lastname: Bai
authors.forename: Mischa
authors.initials: M
authors.lastname: McGibney
authors.forename: Alida R
authors.initials: AR
authors.lastname: Ovrutsky
authors.forename: Edward D
authors.initials: ED
authors.lastname: Chan
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004353:Drug Evaluation, Preclinical; D004777:Environment; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D009161:Mycobacterium / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D009164:Mycobacterium Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D016166:Free Radical Scavengers; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000111:Acetylcysteine
references.citation: Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):947-53
references.pmid: 1554224
references.citation: J Infect. 2009 Nov;59(5):324-31
references.pmid: 19732795
references.citation: Free Radic Biol Med. 2006 Sep 1;41(5):709-21
references.pmid: 16895791
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G877-84
references.pmid: 18239062
references.citation: Emerg Infect Dis. 2009 Oct;15(10):1562-9
references.pmid: 19861046
references.citation: Thorax. 2007 Aug;62(8):661-6
references.pmid: 17311842
references.citation: J Cell Physiol. 2008 Jul;216(1):276-85
references.pmid: 18270969
references.citation: Eur J Immunol. 2006 Jun;36(6):1364-73
references.pmid: 16703568
references.citation: Nat Protoc. 2010 Jan;5(1):51-66
references.pmid: 20057381
references.citation: Free Radic Res. 2009 Dec;43(12):1225-39
references.pmid: 19905985
references.citation: J Biol Chem. 2000 Dec 29;275(52):41000-3
references.pmid: 11042219
references.citation: J Biol Chem. 2004 Aug 6;279(32):33447-55
references.pmid: 15155722
references.citation: Emerg Infect Dis. 2010 Feb;16(2):294-6
references.pmid: 20113563
references.citation: Food Chem Toxicol. 1999 Sep-Oct;37(9-10):949-62
references.pmid: 10541450
references.citation: Am J Respir Cell Mol Biol. 2009 Aug;41(2):170-8
references.pmid: 19097985
references.citation: J Immunol. 2001 Mar 1;166(5):3392-401
references.pmid: 11207296
references.citation: Chest. 2010 Mar;137(3):629-34
references.pmid: 19858235
references.citation: Biol Chem. 2003 Apr;384(4):567-74
references.pmid: 12751786
references.citation: Crit Care. 2009;13(3):411; author reply 411
references.pmid: 19591643
references.citation: Respir Med. 2009 Oct;103(10):1448-55
references.pmid: 19467851
references.citation: Free Radic Res. 2001 Apr;34(4):325-36
references.pmid: 11328670
references.citation: Free Radic Biol Med. 2009 Aug 15;47(4):344-56
references.pmid: 19477268
references.citation: APMIS. 2006 May;114(5):319-28
references.pmid: 16725007
references.citation: Clin Infect Dis. 2009 Dec 15;49(12):e124-9
references.pmid: 19911942