Lipopolysaccharide clustering in colistin persistent and resistant bacteria

Area of Science:

• Microbiology
• Cell Biology
• Antibiotic Resistance

Background:

• Polymyxin antibiotics are crucial for treating Gram-negative bacterial infections.
• Bacterial persistence and mcr-mediated resistance reduce polymyxin efficacy.
• Understanding the mechanisms behind resistance and persistence is vital for developing new therapies.

Purpose of the Study:

• To investigate the nanoscale organization of lipopolysaccharides (LPS) and membrane lipids in persistent and resistant Gram-negative bacteria.
• To compare the membrane organization of colistin-persistent Escherichia coli and Pseudomonas aeruginosa with susceptible cells.
• To identify shared morphological features between bacterial persistence and mcr-1-mediated resistance.

Main Methods:

• Super-resolution localization microscopy was employed to visualize LPS and membrane lipid distribution.
• Analysis focused on colistin-persistent Escherichia coli and Pseudomonas aeruginosa strains.
• Comparison of LPS clustering and membrane organization in susceptible, persistent, and mcr-1-positive bacteria.

Main Results:

• Persister cells showed heterogeneous LPS and membrane lipid distributions with localized LPS clustering.
• Mcr-1-positive E. coli exhibited similar LPS clustering to persisters, without altering overall membrane organization.
• Increased LPS clustering and remodeling were observed in both E. coli and P. aeruginosa, suggesting a shared feature.

Conclusions:

• Bacterial persistence and mcr-1-mediated resistance share a common morphological signature involving envelope reorganisation.
• Localized LPS clustering is a key feature associated with both polymyxin persistence and resistance in Gram-negative bacteria.
• This study provides insights into the structural basis of antibiotic resistance and persistence.