Published June 17, 2020 | Version v1
Journal article Open

Cell Surface Remodeling of Mycobacterium abscessus under Cystic Fibrosis Airway Growth Conditions

Description

Understanding the physiological processes underlying the ability of Mycobacterium abscessus to become a chronic pathogen of the cystic fibrosis (CF) lung is important to the development of prophylactic and therapeutic strategies to better control and treat pulmonary infections caused by these bacteria. Gene expression profiling of a diversity of M. abscessus complex isolates points to amino acids being significant sources of carbon and energy for M. abscessus in both CF sputum and synthetic CF medium, and to the bacterium undergoing an important metabolic reprogramming in order to adapt to this particular nutritional environment. Cell envelope analyses conducted on the same representative isolates further revealed unexpected structural alterations in major cell surface glycolipids known as the glycopeptidolipids (GPLs). Besides showing an increase in triglycosylated forms of these lipids, CF sputum- and synthetic CF medium-grown isolates presented as yet unknown forms of GPLs representing as much as 10 to 20% of the total GPL content of the cells, in which the classical amino alcohol located at the carboxy terminal of the peptide, alaninol, is replaced with the branched-chain amino alcohol, leucinol. Importantly, both these lipid changes were exacerbated by the presence of mucin in the culture medium. Collectively, our results reveal potential new drug targets against M. abscessus in the CF airway and point to mucin as an important host signal modulating the cell surface composition of this pathogen.

Files

acsinfecdis.0c00214.pdf

Files (7.0 MB)

Name Size Download all
md5:dc3b49821b73491d294230280b91dfef
3.7 MB Preview Download
md5:b260c496dbc2de0639478140ac51b536
3.0 MB Preview Download
md5:14fbdca07af200a89c24060e45fb7d7f
280.2 kB Download

Additional details

Funding

LEPVORS – Identification and characterization of new drug resistance and host adaptation mechanisms in Mycobacterium leprae 845479
European Commission