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Nat Rev Microbiol. 2017 Sep;15(9):544-558. doi: 10.1038/nrmicro.2017.59. Epub 2017 Jun 19.

Engineering of obligate intracellular bacteria: progress, challenges and paradigms.

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Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA.
Center of Excellence for Vector-Borne Diseases, Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, USA.
Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture and the Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington 99164, USA.
Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile, Alabama 36688, USA.
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland 21201, USA.
Department of Veterinary Microbiology and Pathology and the Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, 99164, USA.
Vector Borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana 70803, USA.
Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Department for Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27710, USA.
Department of Entomology, University of Minnesota, St. Paul, Minnesota 55108, USA.


It is estimated that approximately one billion people are at risk of infection with obligate intracellular bacteria, but little is known about the underlying mechanisms that govern their life cycles. The difficulty in studying Chlamydia spp., Coxiella spp., Rickettsia spp., Anaplasma spp., Ehrlichia spp. and Orientia spp. is, in part, due to their genetic intractability. Recently, genetic tools have been developed; however, optimizing the genomic manipulation of obligate intracellular bacteria remains challenging. In this Review, we describe the progress in, as well as the constraints that hinder, the systematic development of a genetic toolbox for obligate intracellular bacteria. We highlight how the use of genetically manipulated pathogens has facilitated a better understanding of microbial pathogenesis and immunity, and how the engineering of obligate intracellular bacteria could enable the discovery of novel signalling circuits in host-pathogen interactions.

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