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Engineering of obligate intracellular bacteria: progress, challenges and paradigms

2017; Nature Portfolio; Volume: 15; Issue: 9 Linguagem: Inglês

10.1038/nrmicro.2017.59

1740-1534

Erin E. McClure, Adela S. Oliva Chávez, Dana K. Shaw, Jason A. Carlyon, Roman R. Ganta, Susan M. Noh, David O. Wood, Patrik M. Bavoil, Kelly A. Brayton, Juan J. Martinez, Jere W. McBride, Raphael H. Valdivia, Ulrike G. Munderloh, Joao H. F. Pedra,

Rabies epidemiology and control

In this Review, Pedra and colleagues describe the advances and challenges in the genetic engineering of obligate intracellular bacteria, and highlight examples of how the use of genetically manipulated pathogens has improved our understanding of microbial pathogenesis and host–pathogen interactions. 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.