Uncovering the Contribution of C. burnetii Developmental Stage to Intracellular Pathogenesis

 A defining characteristic of Coxiella burnetii is its developmental cycle, in which the bacterium alternates between two morphologies. In the environment, C. burnetii exists as a small cell variant (SCV), which is a tiny, dense particle that is highly environmentally resistant, and metabolically inert. The SCV is distinct from the large cell variant (LCV), which is larger, intracellular, metabolically active, and replicates by binary fission. SCVs and LCVs differ in their lipid and protein content, and cell wall structure. A common feature of the SCV and LCV is that they are both infectious to cells and embryonated eggs in vitro, however, the respective roles of SCVs and LCVs in the infection of a natural host remains unresolved. Part of the problem is that almost all laboratory models of infection are done with a mixture of both SCVs and LCVs, making it difficult to parse the contribution of the two cell types to the initiation of infection.

 

Our lab is working on a project to separate these two cell types and ask whether they are indeed equally infectious in all cell types. We hypothesize that the SCV's characteristic environmental stability enhances Coxiella's ability to invade and colonize immune cells and cause disease.

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The Developmental Cycle of Coxiella burnetii

When Coxiella is inhaled by a human host it is taken up into the lysosomes of macrophages that reside in the lungs. The environmental form of Coxiella (SCV) is small, dense, and cannot replicate. When the lysosome develops into a spacious Coxiella-containing vacuole (CCV), the SCV changes into Coxiella’s larger, replicating form, the LCV. Over a period of about a week, the macrophage fills up with bacteria, and they begin to change back into their SCV form prior to release for a new round of infection.

Our laboratory is interested in determining if these two different cell types, SCV and LCV, are equally infectious in the context of these immune cells. We also want to know if macrophages activate different defense mechanisms when they are exposed to either SCVs or LCVs.