Mechanical morphotype switching as an adaptive response in mycobacteria.
Haig Alexander EskandarianYu-Xiang ChenChiara TonioloJuan Manuel BelardinelliZuzana PalcekovaLesley HomPaul D AshbyGeorg Ernest FantnerMary JacksonJohn D MckinneyBabak JavidPublished in: Science advances (2024)
Invading microbes face a myriad of cidal mechanisms of phagocytes that inflict physical damage to microbial structures. How intracellular bacterial pathogens adapt to these stresses is not fully understood. Here, we report the discovery of a virulence mechanism by which changes to the mechanical stiffness of the mycobacterial cell surface confer refraction to killing during infection. Long-term time-lapse atomic force microscopy was used to reveal a process of "mechanical morphotype switching" in mycobacteria exposed to host intracellular stress. A "soft" mechanical morphotype switch enhances tolerance to intracellular macrophage stress, including cathelicidin. Both pharmacologic treatment, with bedaquiline, and a genetic mutant lacking uvrA modified the basal mechanical state of mycobacteria into a soft mechanical morphotype, enhancing survival in macrophages. Our study proposes microbial cell mechanical adaptation as a critical axis for surviving host-mediated stressors.
Keyphrases
- atomic force microscopy
- escherichia coli
- microbial community
- cell surface
- single cell
- physical activity
- drug resistant
- stem cells
- high resolution
- genome wide
- small molecule
- reactive oxygen species
- multidrug resistant
- oxidative stress
- gene expression
- pseudomonas aeruginosa
- high throughput
- staphylococcus aureus
- cell therapy
- mental health
- high speed
- antimicrobial resistance
- mass spectrometry
- dna methylation
- gram negative
- mesenchymal stem cells