Genomic DNA of clinical M. abscessus strains

<b>Abstract</b><br/><p><strong>Introduction.</strong> <em>Mycobacterium abscessus</em> (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.</p>
<p><strong>Gap Statement.</strong> 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.</p>
<p><strong>Aim.</strong> This study aimed to investigate the correlation between Mab morphology, GPL, and infectivity by analysing strains from cystic fibrosis patients' sputum samples.</p>
<p><strong>Methodology.</strong> Mab was isolated from patient sputum samples and categorised by morphotype, GPL profile, and replication rate in macrophages. A high-content <em>ex vivo</em> infection model using THP-1 cells assessed the infectivity of both clinical and laboratory strains.</p>
<p><strong>Results.</strong> 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 <em>in vitro</em>, 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.</p>
<p><strong>Conclusion.</strong> 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.</p>