Glycopeptidolipid Genotype Correlates With the Severity of Mycobacterium abscessus Lung Disease

Abstract

Background Smooth and rough colony morphotypes of Mycobacterium abscessus are associated with virulence, but some isolates form both smooth and rough colonies, impeding successful morphotype identification. Reportedly, smooth/rough morphotypes are also related to the glycopeptidolipid (GPL) genotype. However, the accuracy of GPL genotyping to discriminate morphotypes and the relationship between GPL genotype and clinical characteristics of M abscessus lung disease have not been verified. Methods A retrospective analysis of colony morphology, GPL genotype, and clinical data from 182 patients with M abscessus lung disease was conducted. Results Of 194 clinical isolates, 126 (65.0%), 15 (7.7%), and 53 (27.3%) exhibited rough, smooth, and mixed colony morphotypes, respectively. Glycopeptidolipid genotyping indicated that 86.7% (13 of 15) of smooth isolates belonged to the GPL-wild type (WT) group, whereas 98.4% (124 of 126) of rough isolates belonged to the GPL-mutant type (MUT) group. Therefore, GPL genotyping accurately distinguished between smooth and rough morphotypes. Mixed colony morphotypes were also divided into GPL-WT (18.9%) and GPL-MUT (81.1%) groups. Further analysis revealed that patients infected with the GPL-MUT group presented with significantly worse baseline clinical characteristics and exacerbated episodes of lung disease. Conclusions Glycopeptidolipid genotyping accurately distinguishes smooth and rough colony morphotypes. Patients infected with the GPL-MUT genotype exhibit worse clinical characteristics and are at a higher risk of exacerbated lung disease.

Comparison of Isogenic Strains Shows No Evidence of Altered Nosocomial Transmission-Competency of Rough, GPL-Negative Mycobacterium abscessus Strains

“…It has become evident that M. abscessus strains undergo genetic changes within infected hosts, thereby increasing virulence and drug resistance ( 11 , 12 ). Transition from smooth to rough colony morphotypes, most commonly associated with genetic changes leading to a GPL-synthesis defect, is associated with increased virulence and nonremitting, debilitating disease ( 13 ). Recently, a genetic GPL-synthesis defect was reported to be associated with decreased survival of M. abscessus on fomites, suggesting GPL-defect mutations lead to reduced transmissibility ( 1 ).…”

Virulence Mechanisms of Mycobacterium abscessus: Current Knowledge and Implications for Vaccine Design

“…The localization of M. abscessus GPL has been shown to cluster to specific nanodomains on the bacterial surface, ultimately modulating surface hydrophobicity and likely influencing bacterial adhesion and virulence ( Nessar et al, 2011 ; Viljoen et al, 2020 ). The conversion of S to R occur as a result of mutation within genes located within the GPL locus, often associated with GPL synthesis or secretion ( Nessar et al, 2011 ; Pawlik et al, 2013 ; Park et al, 2015 ; Li et al, 2020 ). To date, the mechanisms responsible for S to R conversion are not known; however, this has been hypothesized to occur in response to stress (e.g., Antibiotic stress) which may manifest during host colonization ( Bernut et al, 2016b ; Gutiérrez et al, 2018 ).…”

MAB_2355c Confers Macrolide Resistance in Mycobacterium abscessus by Ribosome Protection

“… M. abscessus is intrinsically resistance to most antimicrobial agents ( 11 , 12 ). Among the few available antibacterial drugs, macrolides are recommended as the treatment of choice due to their anti- M. abscessus activity, as well as their inherent anti-inflammatory and immunomodulatory effects ( 6 , 7 , 13 ).…”