title: Modeling bacterial immune systems: strategies for expression of toxic - but useful - molecules.
abstract: Protection of bacterial cells against virus infection requires expression of molecules that are able to destroy the incoming foreign DNA. However, these molecules can also be toxic for the host cell. In both restriction-modification (R-M), and the recently discovered CRISPR/Cas systems, the toxicity is (in part) avoided through rapid transition of the expression of the toxic molecules from "OFF" to "ON" state. In restriction-modification systems the rapid transition is achieved through a large binding cooperativity, and low translation rate of the control protein. On the other hand, CRISPR array expression in CRISPR/Cas systems involves a mechanism where a small decrease of unprocessed RNAs leads to a rapid increase of processed small RNAs. Surprisingly, this rapid amplification crucially depends on fast non-specific degradation of the unprocessed molecules by an unidentified nuclease, rather than on large cooperativity in protein binding. Furthermore, the major control elements that are responsible for fast transition of R-M and CRISPR/Cas systems from "OFF" to "ON" state, are also directly involved in increased stability of the steady states of these systems. We here discuss mechanisms that allow rapid transition of toxic molecules from the unproductive to the productive state in R-M and CRISPR/Cas systems. The main purpose of this discussion is to put relevant theoretical and experimental work in a perspective that points to general similarities in otherwise mechanistically very different bacterial immune systems.
authors.affiliation: Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia. dmarko@bio.bg.ac.rs
authors.forename: Marko
authors.initials: M
authors.lastname: Djordjevic
mesh_terms: D000465:Algorithms; D001419:Bacteria / Q000235:genetics / Q000276:immunology* / Q000821:virology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001435:Bacteriophages / Q000276:immunology* / Q000502:physiology; D064130:CRISPR-Associated Proteins / Q000235:genetics / Q000276:immunology; D064113:CRISPR-Cas Systems / Q000235:genetics / Q000276:immunology; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics / Q000276:immunology; D015280:DNA Restriction-Modification Enzymes / Q000235:genetics / Q000276:immunology; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D018448:Models, Immunological
chemical_list: D001426:Bacterial Proteins; D064130:CRISPR-Associated Proteins; D015280:DNA Restriction-Modification Enzymes