Spontaneous reversion of Mycobacterium abscessus from a smooth to a rough morphotype is associated with reduced expression of glycopeptidolipid and reacquisition of an invasive phenotype

TLDR

Mycobacterium abscessus is an emerging human pathogen whose virulence determinants are largely unknown, yet a rough wild‑type isolate causes persistent invasive infection while a smooth isogenic mutant lacks this capacity. Serial passage of the smooth mutant produced a spontaneous rough revertant, 390V, that restored the ability to persistently infect human monocytes and mouse lungs. The revertant and the original rough strain exhibit markedly reduced glycopeptidolipid, leading to cord formation and heightened virulence, demonstrating that M.

Abstract

Mycobacterium abscessus is an increasingly important cause of human disease; however, virulence determinants are largely uncharacterized. Previously, it was demonstrated that a rough, wild-type human clinical isolate (390R) causes persistent, invasive infection, while a smooth isogenic mutant (390S) has lost this capability. During serial passage of 390S, a spontaneous rough revertant was obtained, which was named 390V. This revertant regained the ability to cause persistent, invasive infection in human monocytes and the lungs of mice. Glycopeptidolipid (GPL), which plays a role in environmental colonization, was present in abundance in the cell wall of 390S, and was associated with sliding motility and biofilm formation. In contrast, a marked reduction in the amount of GPL in the cell wall of 390R and 390V was correlated with cord formation, a property associated with mycobacterial virulence. These results indicate that the ability to switch between smooth and rough morphologies may allow M. abscessus to transition between a colonizing phenotype and a more virulent, invasive form.