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.

Highlights

  • Mycobacterium abscessus is a rapid growing mycobacterium

  • We identified a gene designated mab_3168c, whose function was unknown, and found that mab_3168c controlled the switching of M. abscessus colony morphology from a rough to a smooth morphotype

  • We showed that loss of mab_3168c expression resulted in alterations in colony morphology, cell surface hydrophobicity, sliding motility, biofilm forming ability, amikacin and lysozyme resistance, and intracellular survivability of M. abscessus

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Summary

Introduction

Mycobacterium abscessus is a rapid growing mycobacterium. It has emerged as an important pathogen of soft tissue, pulmonary, and disseminated infections in both immunocompromised and immunocompetent patients [1,2,3,4]. M. abscessus is one of the most drug-resistant, rapid-growing mycobacteria [2,9,10]. M. abscessus exhibits two different colony morphology types referred to as rough and smooth morphotypes [13,15]. These morphotypes correlate with the virulence of M. abscessus, and cells with a rough morphotype are more virulent

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