Mechanical morphotype switching as an adaptive response in mycobacteria

Area of Science:

• Microbiology
• Cell Biology
• Biophysics

Background:

• Phagocytes employ physical and chemical mechanisms to eliminate invading microbes.
• Intracellular bacterial pathogens' adaptive strategies against host stresses remain incompletely understood.

Purpose of the Study:

• To investigate how intracellular bacterial pathogens adapt to physical stresses imposed by host phagocytes.
• To identify novel virulence mechanisms related to microbial cell surface properties.

Main Methods:

• Long-term time-lapse atomic force microscopy was employed to observe mycobacterial mechanical properties.
• Analysis of bacterial survival and mechanical morphotype switching under host intracellular stress conditions.

Main Results:

• Mycobacteria exhibit a "mechanical morphotype switching" in response to host intracellular stress.
• A "soft" mechanical morphotype enhances tolerance to macrophage-imposed stress, including cathelicidin.
• Pharmacologic treatment (bedaquiline) and genetic mutation (uvrA deletion) induced a soft mechanical morphotype, improving macrophage survival.

Conclusions:

• Microbial cell mechanical adaptation is a critical factor for surviving host-mediated stressors.
• Modulating cell surface stiffness represents a novel virulence strategy for intracellular pathogens.
• Targeting mechanical properties could offer new therapeutic avenues against mycobacterial infections.