title: Subinhibitory Doses of Aminoglycoside Antibiotics Induce Changes in the Phenotype of Mycobacterium abscessus.
abstract: Subinhibitory doses of antibiotics have been shown to cause changes in bacterial morphology, adherence ability, and resistance to antibiotics. In this study, the effects of subinhibitory doses of aminoglycoside antibiotics on Mycobacterium abscessus were investigated. The treatment of M. abscessus cells with subinhibitory doses of amikacin was found to change their colony from a smooth to a rough morphotype and increase their ability to adhere to a polyvinylchloride plate, aggregate in culture, and resist phagocytosis and killing by macrophages. M. abscessus cells treated with a subinhibitory dose of amikacin also became more potent in Toll-like receptor 2 (TLR-2) stimulation, leading to increased tumor necrosis factor alpha (TNF-α) production by macrophages. The MAB_3508c gene was shown to play a role in mediating these phenotypic changes, as its expression in M. abscessus cells was increased when they were treated with a subinhibitory dose of amikacin. In addition, overexpression of MAB_3508c in M. abscessus cells caused changes similar to those induced by subinhibitory doses of amikacin, including a switch from smooth to rough colony morphology, increased ability to aggregate in liquid culture, decreased motility, and increased resistance to killing by macrophages. These findings suggest the importance of using sufficient doses of antibiotics for the treatment of M. abscessus infections.
authors.affiliation: Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Sheng-Hui
authors.initials: SH
authors.lastname: Tsai
authors.affiliation: Department of Medical Biotechnology and Laboratory Sciences and Research Center for Pathogenic Bacteria, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Lai
authors.affiliation: Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China tingnahu@ym.edu.tw.
authors.forename: Shiau-Ting
authors.initials: ST
authors.lastname: Hu
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha