Genomic DNA of clinical M. abscessus strains

Introduction. Mycobacterium abscessus (Mab) is a pathogenic bacterium that
can cause severe lung infections, particularly in individuals with cystic
fibrosis. Mab colonies can exhibit either a smooth (S) or rough (R)
morphotype, influenced by the presence or absence of glycopeptidolipids
(GPL) on their surface, respectively. Despite the clinical significance of
these morphotypes, the relationship between GPL levels, morphotype, and
the pathogenesis of Mab infections remains poorly understood. Gap
Statement. The mechanisms and implications of GPL production and
morphotypes in clinical Mab infections are unclear. There is a gap in
understanding their correlation with infectivity and pathogenicity,
particularly in patients with underlying lung disease. Aim. This study
aimed to investigate the correlation between Mab morphology, GPL, and
infectivity by analysing strains from cystic fibrosis patients'
sputum samples. Methodology. Mab was isolated from patient sputum
samples and categorised by morphotype, GPL profile, and
replication rate in macrophages. A high-content ex vivo infection
model using THP-1 cells assessed the infectivity of both clinical and
laboratory strains. Results. Our findings revealed that around 50% of
isolates displayed mixed morphologies. GPL analysis confirmed a consistent
relationship between GPL content and morphotype was only found only in
smooth isolates. Across morphotype groups, no differences were observed in
vitro, yet clinical R strains were observed to replicate at higher levels
in the THP-1 infection model. Moreover, the proportion of infected
macrophages was notably higher among clinical R strains compared to their
S counterparts at 72 hours post-infection. Clinical variants also infected
THP-1 cells at significantly higher rates compared to laboratory strains,
highlighting the limited translatability of lab strain infection data to
clinical contexts. Conclusion. Our study confirmed the general correlation
between morphotype and GPL levels in smooth strains yet unveiled more
variability within morphotype groups than previously recognised,
particularly during intracellular infection. As the rough morphotype is of
highest clinical concern, these findings contribute to the expanding
knowledge base surrounding Mab infections, offering insights that can
steer diagnostic methodologies, and treatment approaches.