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.