Insights into the CtrA regulon in development of stress resistance in obligatory intracellular pathogen Ehrlichia chaffeensis

Zhihui Cheng, Koshiro Miura, Vsevolod L. Popov, Yumi Kumagai, Yasuko Rikihisa

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35 Scopus citations


Ehrlichia chaffeensis is an obligate intracellular bacterium that causes human monocytic ehrlichiosis. Ehrlichiae have a biphasic developmental cycle consisting of dense-cored cells (DCs) and reticulate cells (RCs). Isolated DCs are more stress resistant and infectious than RCs. Here, we report that a response regulator, CtrA was upregulated in human monocytes at the late growth stage when DCs develop. E.chaffeensis CtrA bound to the promoters of late-stage transcribed genes: ctrA, ompA (peptidoglycan-associated lipoprotein), bolA (stress-induced morphogen) and surE (stationary-phase survival protein), which contain CtrA-binding motifs, and transactivated ompA, surE and bolA promoter-lacZ fusions in Escherichia coli. OmpA was predominantly expressed in DCs. E.chaffeensis binding to and subsequent infection of monocytes were inhibited by anti-OmpA IgG. E.chaffeensis BolA bound to the promoters of genes encoding outer surface proteins TRP120 and ECH_1038, which were expressed in DCs, and transactivated trp120 and ECH_1038 promoter-lacZ fusions. E.chaffeensis bolA complemented a stress-sensitive E.coli bolA mutant. E.coli expressing E.chaffeensis SurE exhibited increased resistance to osmotic stress. Our results suggest that E.chaffeensis CtrA plays a role in co-ordinating development of the stress resistance for passage from the present to the next host cells through its regulon.

Original languageEnglish (US)
Pages (from-to)1217-1234
Number of pages18
JournalMolecular Microbiology
Issue number5
StatePublished - Dec 1 2011


ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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