Morphological remodeling of Coxiella burnetii during its biphasic developmental cycle revealed by cryo-electron tomography
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1.
California Institute of Technology
Abstract
Coxiella burnetii is an obligate zoonotic bacterium that targets macrophages causing a disease called Q fever. It has a biphasic developmental life cycle where the extracellular and metabolically inactive small cell variant (SCV) transforms inside the host into the vegetative large cell variant (LCV). However, details about the morphological and structural changes of this transition are still lacking. Here, we used cryo-electron tomography to image both SCV and LCV variants grown either under axenic conditions or purified directly from host cells. We show that SCVs are characterized by equidistant stacks of inner membrane that presumably facilitate the transition to LCV, a transition coupled with the expression of the Dot/Icm type IVB secretion system (T4BSS). A class of T4BSS particles were associated with extracellular densities possibly involved in host infection. Also, SCVs contained spherical multilayered membrane structures of different sizes and locations suggesting no connection to sporulation as once assumed.
Copyright and License
© 2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Acknowledgement
This project was funded by the National Institutes of Health (grant R01 AI127401 to G.J.J.), an NHMRC grant (APP1196924 to D.G.), and the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (Grant number AI000931-20 to R.A.H. and C.L.L.). D.C.S. is supported by the Melbourne Research Scholarship. We are grateful to Prof. Elitza Tocheva for insightful discussions, and Somavally Dalvi for her help with figure preparation.
Contributions
Conceptualization, D.G., G.J.J., and M.K.; Methodology, D.G., M.K., D.C.S., C.L.L., P.D., P.A.B., and E.K.; Investigation, M.K., D.G., D.C.S., C.L.L., P.D., and P.A.B.; Formal Analysis, M.K., D.G., D.C.S., C.L.L., P.D., P.A.B., K.W.K., N.V., E.K., and R.A.H.; Writing – Original Draft, D.G., M.K., and N.V.; Writing – Review and Editing, M.K., D.G., D.C.S., C.L.L., P.D., P.A.B., K.W.K., N.V., E.K., R.A.H., and G.J.J.; Visualization, M.K., D.G., and D.C.S.; Supervision, G.J.J. and D.G.; Funding Acquisition, G.J.J. and D.G.
Data Availability
• The subtomogram averages have been deposited to EMBD (EMD-28281, EMD-28282 and EMD-28283) and will be publicly accessible. The raw data is available upon request.
• This paper does not report original code.
• Any additional information required to reanalyze the data presented in this study is available from the lead contact upon request.
Conflict of Interest
The authors declare no competing interests.
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Additional details
- PMCID
- PMC10362272
- National Institutes of Health
- R01 AI127401
- National Health and Medical Research Council
- APP1196924
- National Institutes of Health
- AI000931-20
- University of Melbourne
- Caltech groups
- Division of Biology and Biological Engineering