Mechanical morphotype switching as an adaptive response in mycobacteria

Author:

Eskandarian Haig Alexander12ORCID,Chen Yu-Xiang1ORCID,Toniolo Chiara3ORCID,Belardinelli Juan M.4ORCID,Palcekova Zuzana4ORCID,Hom Lesley1ORCID,Ashby Paul D.25ORCID,Fantner Georg E.6ORCID,Jackson Mary4ORCID,McKinney John D.3ORCID,Javid Babak1ORCID

Affiliation:

1. Division of Experimental Medicine, University of California San Francisco, San Francisco, CA 94143, USA.

2. Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

3. School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), 1015 Lausanne, Switzerland.

4. Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.

5. Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

6. School of Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.

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 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.

Publisher

American Association for the Advancement of Science (AAAS)

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