Meso-tartrate inhibits intracellular replication of Coxiella burnetii, the causative agent of the zoonotic disease Q fever.

The zoonotic disease Q fever, caused by the intracellular bacterium Coxiella burnetii, remains a global health threat due to its high infectivity, environmental stability, the debilitating nature of the disease and the long duration of treatment. Designing new and potent drugs that target previously unexplored pathways is essential to shorten treatment time and minimize antibiotic resistance. Nicotinamide adenine dinucleotide (NAD) is an essential and ubiquitous cofactor in all living organisms. NadB, an L-aspartate oxidase catalysing the first step of the prokaryotic-specific NAD de novo biosynthetic pathway, is required for C. burnetii growth and replication inside host cells. In this study, in vitro enzyme assays utilising recombinant GST-NadB demonstrated inhibition of the L-aspartate oxidase activity of NadB by meso-tartrate. Furthermore, meso-tartrate inhibits intracellular growth and replication of C. burnetii inside host cells in a dose-dependent manner, and has no effect on the viability of mammalian cells. Unexpectedly, meso-tartrate also inhibited growth of C. burnetii in axenic medium, and further reduces replication of the nadB mutant inside host cells, suggesting it is acting more widely than simple inhibition of NadB. Overall these results suggest that the anti-bacterial activity of meso-tartrate warrants further study, including investigation of its additional target(s).