Abstract

Mycobacterium abscessus is emerging as a cause of recalcitrant chronic pulmonary infections, particularly in people with cystic fibrosis (CF). Biofilm formation has been implicated in the pathology of this organism, however the role of biofilm formation in infection is unclear. Two colony-variants of M. abscessus are routinely isolated from CF samples, smooth (MaSm) and rough (MaRg). These two variants display distinct colony morphologies due to the presence (MaSm) or absence (MaRg) of cell wall glycopeptidolipids (GPLs). We hypothesized that MaSm and MaRg variant biofilms might have different mechanical properties. To test this hypothesis, we performed uniaxial mechanical indentation, and shear rheometry on MaSm and MaRg colony-biofilms. We identified that MaRg biofilms were significantly stiffer than MaSm under a normal force, while MaSm biofilms were more pliant compared to MaRg, under both normal and shear forces. Furthermore, using theoretical indices of mucociliary and cough clearance, we identified that M. abscessus biofilms may be more resistant to mechanical forms of clearance from the lung, compared to another common pulmonary pathogen, Pseudomonas aeruginosa. Thus, the mechanical properties of M. abscessus biofilms may contribute to the persistent nature of pulmonary infections caused by this organism.

Highlights

  • Mycobacterium abscessus is emerging as a cause of recalcitrant chronic pulmonary infections, in people with cystic fibrosis (CF)

  • To test the hypothesis that biofilms of MaSm and MaRg variants might differ in their mechanical properties, uniaxial indentation and shear rheology was performed on 4 day M. abscessus colony-biofilms (See Supplementry Methods)

  • We set out to analyze the mechanical properties of M. abscessus in vitro biofilms to gain a better understanding of the biofilm biology of this organism

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Summary

Introduction

Mycobacterium abscessus is emerging as a cause of recalcitrant chronic pulmonary infections, in people with cystic fibrosis (CF). In the cystic fibrosis (CF) lung, due to genetic mutations in the cystic fibrosis transmembrane regulator (CFTR) ion channel responsible for this disease, the mucus lining of the airways becomes dehydrated and highly viscous, leading to impaired clearance and accumulation This provides a niche that can be readily colonized by inhaled microorganisms, which form biofilm aggregates within the accumulated mucus ­layer[1,2]. We hypothesized that the biofilms of MaSm and MaRg may have different mechanical properties, due to their distinct colony morphologies, and that these properties may help to account for the persistence of infection caused by this organism. Our findings support the hypothesis that biofilm viscoelasticity could contribute to the persistence of biofilm-associated ­infefctions[15,19], and provides novel insight into why M. abscessus may be such a persistent pathogen in airway infection in people with CF

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