MtvS Regulates the Francisella Type V-A CRISPR-Cas System

CRISPR-Cas systems endow bacteria and archaea with adaptive immune systems against mobile genetic elements, playing a fundamental role in shaping microbial communities. Many organisms harbor more than one CRISPR-Cas system, however whether and how these are differentially regulated is not known, in many instances due to the impossibility of studying CRISPR immunity in native hosts. Here we studied the regulation of endogenous type II-B and type V-A CRISPR-Cas systems in opportunistic human pathogen Francisella novicida U112. Fluorescence microscopy and transcriptomics experiments revealed that while the type II-B system is constitutively expressed, the type V-A CRISPR-Cas system is differentially expressed at stationary phase and high cell density. Using mass spectrometry and genetics we identified MtvS as a factor required for the differential expression of the type V-A CRISPR-Cas locus. Surprisingly, MtvS-dependent expression of the type V-A CRISPR-Cas system at high cell density is linked quorum sensing like behavior, even though F. novicida U112 lacks canonical quorum sensing genes. Our findings provide an example of how bacteria harboring multiple CRISPR systems regulate their expression.