Role of adipose triglyceride lipase and CGI-58 in lipid droplet breakdown during Coxiella burnetii infection
Dr. Minal Mulye, Ph.D.
Medicine and Health Sciences
Coxiella burnetii is an obligate intracellular bacterium responsible for causing culture negative endocarditis. The manifestation of this condition several years following initial infection exhibits Coxiella’s ability to persist long-term in alveolar macrophages. Our overall goal is to identify the strategies Coxiella employs for successful survival in the host. In our previous studies, examination of Coxiella-infected alveolar macrophages revealed accumulation of host lipid storage organelles called lipid droplets (LDs). Host LD alteration was dependent on Coxiella Type 4 Secretion System (T4SS) which re-leases bacterial proteins in the host cytoplasm and manipulates several host cell processes. Further, manipulating LD metabolism significantly altered Coxiella growth. Specifically blocking the activity of the LD breakdown enzyme adipose triglyceride li-pase (ATGL) completely inhibited Coxiella growth suggesting that ATGL-mediated LD catabolism is important for bacterial intracellular survival. Based on our preliminary studies, we hypothesize that Coxiella manipulates host cell ATGL to promote LD breakdown and support intracellular bacterial growth. To test this, we quantitated ATGL gene expression level in uninfected, wild-type Coxiella-infected and T4SS-mutant Coxi-ella-infected alveolar macrophages. Compared to uninfected cell, Coxiella-infected cells demonstrated increased ATGL gene expression in a T4SS-dependent manner suggesting importance of ATGL during Coxiella infection. Since ATGL activity depends on co-activator CGI-58 binding, we determined CGI-58 gene expression levels in differentially infected cells. However, no differences were observed in CGI-58 suggesting that Coxiella specifically manipulates ATGL via its T4SS and not its co-activator. On-going studies are determining if Coxiella manipulates ATGL protein level and activity. Completion of our studies will identify the mechanism Coxiella employs to manipulate host LD homeostasis to promote its intracellular survival.
Copyright 2019 all authors
Newman, Michael J. OMS-2; Silliman, Rachel OMS-3; and Mulye, Minal Ph.D, "Role of adipose triglyceride lipase and CGI-58 in lipid droplet breakdown during Coxiella burnetii infection" (2019). MU-COM Research Day. 149.