Engineering of Obligate Intracellular Bacteria: Progress, Challenges and Paradigms

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

Abstract

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.

Publication types

  • Review

MeSH terms

  • Bacterial Infections / genetics*
  • Bacterial Infections / immunology*
  • Bacterial Infections / pathology
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / immunology
  • DNA, Bacterial / immunology*
  • Genetic Engineering*
  • Genome, Bacterial / immunology
  • Host-Pathogen Interactions / genetics*
  • Host-Pathogen Interactions / immunology*
  • Humans

Substances

  • Bacterial Toxins
  • DNA, Bacterial