EirA Is a Novel Protein Essential for Intracellular Replication of Coxiella burnetii.

The zoonotic bacterial pathogen is the causative agent of Q fever, a febrile illness which can cause a serious chronic infection. is a unique intracellular bacterium which replicates within host lysosome-derived vacuoles. The ability of to replicate within this normally hostile compartment is dependent on the activity of the Dot/Icm type 4B secretion system. In a previous study, a transposon mutagenesis screen suggested that the disruption of the gene encoding the novel protein CBU2072 rendered incapable of intracellular replication. This protein, subsequently named EirA (ssential for ntracellular eplication A), is indispensable for intracellular replication and virulence, as demonstrated by infection of human cell lines and infection of The putative N-terminal signal peptide is essential for protein function but is not required for localization of EirA to the bacterial inner membrane compartment and axenic culture supernatant. In the absence of EirA, remains viable but nonreplicative within the host phagolysosome, as coinfection with expressing native EirA rescues the replicative defect in the mutant strain. In addition, while the bacterial ultrastructure appears to be intact, there is an altered metabolic profile shift in the absence of EirA, suggesting that EirA may impact overall metabolism. Most strikingly, in the absence of EirA, Dot/Icm effector translocation was inhibited even when EirA-deficient replicated in the wild type (WT)-supported containing vacuoles. EirA may therefore have a novel role in the control of Dot/Icm activity and represent an important new therapeutic target.