Importance of fatty acid binding protein 4 (FABP4) during Coxiella burnetti intracellular growth in alveolar macrophages

Coxiella burnetti is an obligate intracellular bacterial pathogen that spreads to humans via inhalation, infects alveolar macrophages and causes the worldwide zoonosis known as Q fever. Acutely, Coxiella infection manifests as a mild flu-like illness. However, chronic disease presents as endocarditis which is fatal if untreated. It is often clinically undetected until as many as 20 years post-infection suggesting Coxiella’s ability to manipulate host cell processes to establish long-term survival. Although Coxiella initial-ly infects alveolar macrophages, in endocarditis patients it is found in lipid droplet (LD)-rich foam cells. Our previous studies demonstrate that Coxiella manipulates host lipid storage organelle LD accumulation by releasing bacterial effector proteins via its major virulence factor Type 4 secretion system (T4SS). Further, manipulation of host cell LD homeostasis significantly alters Coxiella intracellular growth suggesting the importance of LDs during Coxiella infection. Our overall goal is to identify host cell proteins Coxiella targets to manipulate host cell LD metabolism. Fatty acid binding protein 4 (FABP4) is a cytoplasmic fatty acid chaperone expressed primarily in adipocytes and macrophag-es. It regulates intracellular lipid accumulation and plays an important role in foam cell formation during atherosclerosis. Since LD metabolism plays an essential role during Coxiella pathogenesis, we hypothesize that Coxiella manipulates FABP4 to promote LD accumulation in Coxiella-infected cells. To address this, we performed quantitative Real Time PCR (qRT-PCR) to determine Fabp4 expression in Coxiella-infected alveo-lar macrophages. Compared to uninfected cells, Fabp4 gene expression significantly increased in Coxiella-infected cells suggesting its importance during bacterial infection of alveolar macrophages. Ongoing studies are determining if Coxiella actively manipu-lates FABP4 gene expression via T4SS effectors. Future studies will identify the role of FABP4 in LD accumulation in Coxiella-infected alveolar macrophages and measure bacterial growth in Fabp4-/- alveolar macrophages