Abstract
Mycobacterium abscessus is a non-tuberculous mycobacterium. It can cause diseases in both immunosuppressed and immunocompetent patients and is highly resistant to multiple antimicrobial agents. M. abscessus displays two different colony morphology types: smooth and rough morphotypes. Cells with a rough morphotype are more virulent. The purpose of this study was to identify genes responsible for M. abscessus morphotype switching. With transposon mutagenesis, a mutant with a Tn5 inserted into the promoter region of the mab_3168c gene was found to switch its colonies from a rough to a smooth morphotype. This mutant had a higher sliding motility but a lower ability to form biofilms, aggregate in culture, and survive inside macrophages. Results of bioinformatic analyses suggest that the putative Mab_3168c protein is a member of the GCN5-related N-acetyltransferase superfamily. This prediction was supported by the demonstration that the mab_3168c gene conferred M. abscessus and M. smegmatis cells resistance to amikacin. The multiple roles of mab_3168c suggest that it could be a potential target for development of therapeutic regimens to treat diseases caused by M. abscessus.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetyltransferases / genetics*
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Acetyltransferases / metabolism*
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Amikacin / pharmacology
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Anti-Infective Agents / pharmacology
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Biofilms / growth & development
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Computational Biology / methods
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Drug Resistance, Microbial / genetics*
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Hydrophobic and Hydrophilic Interactions / drug effects
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Macrophages / metabolism
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Muramidase / drug effects
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Muramidase / genetics
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Muramidase / metabolism
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Mutation / genetics
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Mycobacterium / drug effects
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Mycobacterium / enzymology*
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Mycobacterium / genetics
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Mycobacterium / metabolism
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Mycobacterium Infections, Nontuberculous / drug therapy
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Mycobacterium Infections, Nontuberculous / enzymology*
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Mycobacterium Infections, Nontuberculous / genetics
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Mycobacterium Infections, Nontuberculous / metabolism
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Nontuberculous Mycobacteria / drug effects
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Nontuberculous Mycobacteria / enzymology*
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Nontuberculous Mycobacteria / genetics
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Nontuberculous Mycobacteria / metabolism
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Promoter Regions, Genetic / genetics
Substances
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Anti-Infective Agents
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Amikacin
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Acetyltransferases
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Muramidase
Grants and funding
This work was supported by grant NSC 99-2320-B-006-MY3 from the National Science Council, Taiwan, ROC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.