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STACEY GILK, PhD EDUCATION |
RESEARCH INTEREST
We are interested in how intracellular pathogens manipulate host cell lipids and lipid metabolism in order to establish the intracellular niche. We study the obligate intracellular bacterium Coxiella burnetii, a highly infectious pathogen which is considered a potential bioterrorism weapon. Coxiella replicates insides a highly specialized lysosome-like vacuole known as the Coxiella containing vacuole (CCV). My team recently discovered that the bacteria is very sensitive to CCV cholesterol levels, with elevated cholesterol leading to increased CCV acidification and bacterial degradation. Because cholesterol readily traffics to the CCV and is found in the CCV membrane, we hypothesize that Coxiella regulates CCV cholesterol levels in order to maintain the optimal CCV environment. We are currently investigating two Coxiella-driven mechanisms to lower CCV cholesterol. First, Coxiella recruits a host cholesterol-binding protein, ORP1L, to the CCV; ORP1L mediates membrane contact sites between the CCV and the host endoplasmic reticulum. We are characterizing the formation and function of these membrane contact sites, and determining whether they have a role in transferring cholesterol from the CCV to the ER. Second, Coxiella expresses a sterol modifying enzyme, CBU1206. A CBU1206 mutant grows poorly in cells, is hypersensitive to cellular cholesterol, and has elevated cholesterol in the CCV. We are currently investigating the enzymatic activity of CBU1206 as well as a second putative Coxiella sterol-modifying enzyme, CBU1158.
REPRESENTATIVE PUBLICATIONS
Samanta D, Clemente T, Schuler B, and SD Gilk. Coxiella burnetii Type 4B Secretion System-dependent manipulation of endolysosomal maturation is required for bacterial growth. 2019. PLoS Pathogens Dec 23;15(12):e1007855. doi: 10.1371/journal.ppat.1007855.
Cockburn C, Green R, Damle S, Martin R, Ghahrai N, Colonne P, Fullerton M, Conrad D, Chalfant, C, Voth D, Rucks E, Gilk SD, and J Carlyon. 2019. Functional inhibition of acid sphingomyelinase disrupts infection by intracellular bacteria. Life Sciences Alliance Mar 22;2(2). doi: 10.26508/lsa.201800292.
Mulye M, Zapata B, and SD Gilk. 2018. Altering LD homeostasis in alveolar macrophages affects Coxiella burnetii intracellular growth. PLoS One 2018 Feb 1;13(2):e0192215. doi: 10.1371/journal.pone.0192215.
Samanta D, and SD Gilk. 2017. Measuring pH of the Coxiella burnetii parasitophorous vacuole. Current Protocols in Microbiology, Nov 9; 47:6C.3.1-6C.3.11. doi: 10.1002/cpmc.38.
Mulye M, Samanta D, Heinzen RA, and SD Gilk. 2017. Elevated cholesterol in the Coxiella burnetii intracellular niche is bacteriolytic. mBio Feb 28;8(1). doi: 10.1128/mBio.02313-16.
Justis AV, Hansen B, Beare PA, King KB, Heinzen RA, and SD Gilk. 2017. Interactions between the Coxiella burnetii parasitophorous vacuole and the endoplasmic reticulum involve the host protein ORP1L. Cellular Microbiology Jan;19(1). doi: 10.1111/cmi.12637. Epub 2016 Jul 15
Gilk SD, Cockrell DA, Luterbach C, Hansen B, Knodler L, Steele-Mortimer O, and RA Heinzen. 2013. Bacterial colonization of host cells in the absence of cholesterol. PLoS Pathogens Jan; 9(1): e1003107