Mechanical morphotype switching as an adaptive response in mycobacteria

Eskandarian, H. A.; Chen, Y.-X.; Toniolo, C.; Belardinelli, J. M.; Palcekova, Z.; Ashby, P. D.; Fantner, G. E.; Jackson, M.; McKinney, J. D.; Javid, B.

doi:10.1101/2022.04.06.487411

bioRxiv · 10.1101/2022.04.06.487411

Mechanical morphotype switching as an adaptive response in mycobacteria

Eskandarian, H. A.·Chen, Y.-X.·Toniolo, C.·Belardinelli, J. M.·Palcekova, Z.·Ashby, P. D.·Fantner, G. E.·Jackson, M.·McKinney, J. D.·Javid, B.

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Abstract

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 a new virulence mechanism by which mycobacteria alter the mechanical stiffness of their cell surface to become refractory 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. Genetic manipulation, by deletion of uvrA, or pharmacological treatment, with bedaquiline, locked mycobacteria into a "soft" mechanical morphotype state, enhancing survival in macrophages. Our study proposes microbial mechanical adaptation as a new axis for surviving host-mediated stressors. One-Sentence SummaryBacteria alter their cell surface mechanical properties to increase survival during macrophage infection.

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Eskandarian, H. A., Chen, Y.-X., Toniolo, C., Belardinelli, J. M., Palcekova, Z., Ashby, P. D., Fantner, G. E., Jackson, M., McKinney, J. D., Javid, B.. 2022-04-07. Mechanical morphotype switching as an adaptive response in mycobacteria. https://doi.org/10.1101/2022.04.06.487411

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