A Coxiella burnetii gene encodes a sensor-like protein

Two-component regulatory systems play important roles in the adaptive responses of many bacteria to environmental changes. The sensor proteins of these systems are highly conserved near their C-termini. We exploited this feature to isolate a gene encoding a putative sensor component from the obligate intracellular rickettsial parasite Coxiella burnetii (Cb). Using degenerate primers and the polymerase chain reaction (PCR), we isolated a DNA fragment from a genomic library of Cb containing an open reading frame (ORF), sufficient to encode a 48-kDa protein. Sequence comparison revealed that the deduced protein shared high homology to members of the bacterial sensor protein family, particularly at three conserved regions of the C terminus. When the Cb sensor-like gene was cloned into a high-copy-number vector and introduced into an E. coli strain (phoM, phoR), the mutant expressed low levels of alkaline phosphatase activity, suggesting that the gene functioned as a sensor protein in E. coli. Consequently, we designated this gene qrsA (for Q fever agent regulatory sensor-like gene). Because two-component regulatory systems have been implicated in a variety of cellular processes, including virulence determinants in some pathogenic bacteria, the identification of qrsA in Cb may shed light on how the pathogen adapts to extracellular changes during infection, as it proliferates in the phagolysosome.