Record Details
Essential Role for the Response Regulator PmrA in Coxiella burnetii Type 4B Secretion and Colonization of Mammalian Host Cells
ScholarsArchive at Oregon State University
| Field | Value |
|---|---|
| Title | Essential Role for the Response Regulator PmrA in Coxiella burnetii Type 4B Secretion and Colonization of Mammalian Host Cells |
| Names |
Beare, Paul A.
(creator) Sandoz, Kelsi M. (creator) Larson, Charles L. (creator) Howe, Dale (creator) Kronmiller, Brent (creator) Heinzen, Robert A. (creator) |
| Date Issued | 2014-06 (iso8601) |
| Note | To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. The published article is copyrighted by the American Society for Microbiology and can be found at: http://jb.asm.org/. |
| Abstract | Successful host cell colonization by the Q fever pathogen, Coxiella burnetii, requires translocation of effector proteins into the host cytosol by a Dot/Icm type 4B secretion system (T4BSS). In Legionella pneumophila, the two-component system (TCS) PmrAB regulates the Dot/Icm T4BSS and several additional physiological processes associated with pathogenesis. Because PmrA consensus regulatory elements are associated with some dot/icm and substrate genes, a similar role for PmrA in regulation of the C. burnetii T4BSS has been proposed. Here, we constructed a C. burnetii pmrA deletion mutant to directly probe PmrA-mediated gene regulation. Compared to wild-type bacteria, C. burnetii ΔpmrA exhibited severe intracellular growth defects that coincided with failed secretion of effector proteins. Luciferase gene reporter assays demonstrated PmrA-dependent expression of 5 of 7 dot/icm operons and 9 of 11 effector-encoding genes with a predicted upstream PmrA regulatory element. Mutational analysis verified consensus sequence nucleotides required for PmrA-directed transcription. RNA sequencing and whole bacterial cell mass spectrometry of wild-type C. burnetii and the ΔpmrA mutant uncovered new components of the PmrA regulon, including several genes lacking PmrA motifs that encoded Dot/Icm substrates. Collectively, our results indicate that the PmrAB TCS is a critical virulence factor that regulates C. burnetii Dot/Icm secretion. The presence of PmrA-responsive genes lacking PmrA regulatory elements also suggests that the PmrAB TCS controls expression of regulatory systems associated with the production of additional C. burnetii proteins involved in host cell parasitism. |
| Genre | Article |
| Identifier | Beare, P. A., Sandoz, K. M., Larson, C. L., Howe, D., Kronmiller, B., & Heinzen, R. A. (2014). Essential role for the response regulator PmrA in Coxiella burnetii type 4B secretion and colonization of mammalian host cells. Journal of Bacteriology, 196(11), 1925-1940. doi:10.1128/JB.01532-14 |
