title: I can see CRISPR now, even when phage are gone: a view on alternative CRISPR-Cas functions from the prokaryotic envelope.
abstract: OBJECTIVE
  CRISPR-Cas systems are prokaryotic immune systems against invading nucleic acids that adapt as new environmental threats arise. There are emerging examples of CRISPR-Cas functions in bacterial physiology beyond their role in adaptive immunity. This highlights the poorly understood, but potentially common, moonlighting functions of these abundant systems. We propose that these noncanonical CRISPR-Cas activities have evolved to respond to stresses at the cell envelope.
  
  
  RESULTS
  Here, we discuss recent literature describing the impact of the extracellular environment on the regulation of CRISPR-Cas systems, and the influence of CRISPR-Cas activity on bacterial physiology. These described noncanonical CRISPR-Cas functions allow the bacterial cell to respond to the extracellular environment, primarily through changes in envelope physiology.
  
  
  CONCLUSIONS
  This review discusses the expanding noncanonical functions of CRISPR-Cas systems, including their roles in virulence, focusing mainly on their relationship to the cell envelope. We first examine the effects of the extracellular environment on regulation of CRISPR-Cas components, and then discuss the impact of CRISPR-Cas systems on bacterial physiology, concentrating on their roles in influencing interactions with the environment including host organisms.
authors.affiliation: aDepartment of Microbiology and Immunology, Microbiology and Molecular Genetics Program bEmory Vaccine Center cYerkes National Primate Research Center, Atlanta, Georgia dDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California eDepartment of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA *Hannah K. Ratner and Dr Timothy R. Sampson contributed equally to the writing of this article.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Ratner
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sampson
authors.forename: David S
authors.initials: DS
authors.lastname: Weiss
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D000914:Antibodies, Viral / Q000276:immunology*; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology*; D064113:CRISPR-Cas Systems / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D010802:Phylogeny; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014759:Viral Envelope Proteins