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Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), linkedwith CRISPR associated (CAS) genes, play a profound role in the interactionsbetween phage and their bacterial hosts. It is now well understood thatCRISPR-CAS systems can confer adaptive immunity against bacteriophageinfections. However, the possibility of failure of CRISPR immunity may lead toa productive infection by the phage (cell lysis) or lysogeny. Recently,CRISPR-CAS genes have been implicated in changes to group behaviour, includingbiofilm formation, of the bacterium Pseudomonas aeruginosa when lysogenized.For lysogens with a CRISPR system, another recent experimental study suggeststhat bacteriophage re-infection of previously lysogenized bacteria may lead tocell death. Thus CRISPR immunity can have complex effects on phage-host-lysogeninteractions, particularly in a biofilm. In this contribution, we develop andanalyse a series of models to elucidate and disentangle these interactions.From a therapeutic standpoint, CRISPR immunity increases biofilm resistance tophage therapy. Our models predict that lysogens may be able to displaceCRISPR-immune bacteria in a biofilm, and thus suggest strategies to eliminatephage resistant biofilms.

Mathematical Modeling of CRISPR-CAS system effects on biofilm formation