Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

Abstract

Invasion of macrophages and replication within an acidic and degradative phagolysosome-like vacuole are essential for disease pathogenesis by Coxiella burnetii, the bacterial agent of human Q fever. Previous experimental constraints imposed by the obligate intracellular nature of Coxiella limited knowledge of pathogen strategies that promote infection. Fortunately, new genetic tools facilitated by axenic culture now allow allelic exchange and transposon mutagenesis approaches for virulence gene discovery. Phenotypic screens have illuminated the critical importance of Coxiella's type 4B secretion system in host cell subversion and discovered genes encoding translocated effector proteins that manipulate critical infection events. Here, we highlight the cellular microbiology and genetics of Coxiella and how recent technical advances now make Coxiella a model organism to study macrophage parasitism.

KEYWORDS:

• apoptosis
• autophagy
• Coxiella burnetii
• effector protein
• host cell invasion
• macrophages
• mutagenesis
• phagolysosome
• type 4B secretion
• vacuole remodeling

Supplementary Data

Acknowledgements

The authors thank A Mora for graphics support and B Hansen for electron microscopy.

Financial & competing interests disclosure

This work was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (RA Heinzen) and by grants from the Agence Nationale de la Recherche (ANR) (ANR-14-CE14-0012-01; Project AttaQ), ERA-NET Infect-ERA (ANR-13-IFEC-0003; Project EUGENPATH) and the ATIP-AVENIR programme (M Bonazzi). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (RA Heinzen) and by grants from the Agence Nationale de la Recherche (ANR) (ANR-14-CE14-0012-01; Project AttaQ), ERA-NET Infect-ERA (ANR-13-IFEC-0003; Project EUGENPATH) and the ATIP-AVENIR programme (M Bonazzi). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.