A Simple In Vitro Method to Determine Bactericidal Activity Against Mycobacterium abscessus Under Hypoxic Conditions

Area of Science:

• Microbiology
• Drug Discovery
• Antimicrobial Resistance

Background:

• Non-replicating persisters (NRPs) of Mycobacterium abscessus are a resilient bacterial subpopulation contributing to treatment failure.
• These persistent bacteria survive host conditions like hypoxia and nutrient starvation, complicating eradication efforts.

Purpose of the Study:

• To develop and validate a model for generating and studying low-oxygen persisters (LOPs) of M. abscessus.
• To identify potential drug candidates effective against these persistent bacterial forms.

Main Methods:

• Generation of M. abscessus LOPs using a controlled hypoxic environment in microtiter plates.
• Assessment of LOP characteristics including replication rates, reversibility, and morphological changes via colony counting and microscopy.
• Screening of known antimycobacterial agents for bactericidal activity against LOPs.

Main Results:

• The generated LOPs exhibited reduced replication, reversible persistence, delayed regrowth, and altered morphology.
• Significant phenotypical resistance to several clinically relevant antimycobacterial compounds was observed.
• Metronidazole and niclosamide demonstrated bactericidal activity against M. abscessus LOPs.

Conclusions:

• The developed model is effective for identifying compounds active against hypoxic persisters.
• This approach can accelerate the discovery of novel antimycobacterial drugs targeting persistent bacterial infections.
• The model serves as a valuable tool in the drug development pipeline for challenging infections like M. abscessus.