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Title: Mechanical morphotype switching as an adaptive response in mycobacteria

Journal Article · · Science Advances
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [4]; ORCiD logo [5]; ORCiD logo [6]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [3]; ORCiD logo [5]
  1. Univ. of California, San Francisco, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Harvard Medical School, Boston, MA (United States)
  2. Univ. of California, San Francisco, CA (United States); Stanford Univ., CA (United States)
  3. Ecole Polytechnique Federale Lausanne (EPFL) (Switzerland)
  4. Colorado State Univ., Fort Collins, CO (United States)
  5. Univ. of California, San Francisco, CA (United States)
  6. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Molecular Foundry

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
2337825
Journal Information:
Science Advances, Journal Name: Science Advances Journal Issue: 1 Vol. 10; ISSN 2375-2548
Publisher:
AAASCopyright Statement
Country of Publication:
United States
Language:
English

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