Characterizing strain-specific host-pathogen interactions that modulate Coxiella burnetii infection

Authors

• MU Ahmed
• T Dorsey
• S Ambs

Abstract

Coxiella burnetii is a gram-negative intracellular bacterium that causes the human disease Q fever, which can present as an acute flu-like illness or persistent, focalized infection. Mammals, including livestock, are a natural reservoir for C. burnetii and most human infections are acquired by inhalation of contaminated aerosols derived from these animals. Despite the presence of full-length, phase I lipopolysaccharide (LPS), C. burnetii Dugway strains, isolated in 1957 from the Dugway Proving Grounds, Utah, USA, have been reported to exhibit attenuation in vivo. In addition to LPS, the C. burnetii Dot/Icm type 4 secretion system (T4SS) is an important virulence determinant that delivers effector proteins required for the development of the Coxiella-containing vacuole and bacterial replication. Genome sequencing has revealed numerous genes encoding putative effector proteins that are unique to Dugway. These genes were assayed for bacterial secretion using an adenylate cyclase reporter assay and 13 out of 61 putative effectors tested were actively secreted. To further characterize the confirmed secreted effector proteins, fluorescently tagged Dugway effector proteins are currently being tested in mammalian ectopic expression assays. Preliminary results have demonstrated differences in effector localization patterns suggesting, in some cases, specific host-effector interactions. RNA sequencing of human monocytic cells infected with either virulent nine mile I (NMI) or Dugway showed that Dugway-infected cells had distinct gene expression patterns compared to cells infected with NMI, particularly in genes associated with innate inflammatory responses. This research will provide important information about the specific mechanisms and host-pathogen interactions that promote C. burnetii virulence.

Scientific Focus Area: Microbiology and Infectious Diseases

This page was last updated on Monday, September 25, 2023