Coxiella burnetii: Hiding in Plain Sight

The intracellular bacterial pathogen Coxiella burnetii causes the zoonotic disease Q fever. Due to the combined traits of a very low infectious dose, significant environmental resistance, and the debilitating consequences of infection, this pathogen is considered source material for a potential biological weapon. Q fever has non-specific clinical presentation and can include both acute and life-threatening chronic sequelae. A recent outbreak of Q fever in the Netherlands, propagated by widespread infection of farmed goats, has highlighted that C. burnetii represents an important biological threat to public health but can also have a significant economic and environmental impact on agricultural industry. C. burnetii is an intravacuolar pathogen that replicates to extremely high numbers within a membrane-bound compartment termed the Coxiella-containing vacuole (CCV). Recent studies into the metabolic requirements of C. burnetii allowed researchers to develop an axenic culture media to propagate C. burnetii in a cell-free system. This advance has revolutionized research into this neglected pathogen, paving the way for application of genetic manipulation and mutagenesis studies to identify the key virulence factors of C. burnetii. Central to the capacity of C. burnetii to replicate inside eukaryotic cells, and cause disease, is the Dot/Icm type IV secretion system. This protein translocation apparatus enables C. burnetii to introduce over 140 virulence proteins, termed effectors, into the host cell. The collective action of these effectors remodels the host to maintain viability and support intracellular replication of C. burnetii. Future functional characterization of these important effectors will facilitate understanding of how C. burnetii causes disease and may aid development of novel therapeutic and preventative actions that will minimize the impact of both natural and deliberate Q fever outbreaks.