Ali Qasim, Wahl Lindi M
a Department of Applied Mathematics , University of Western Ontario , London , ON , Canada.
J Biol Dyn. 2017 Aug;11(sup2):264-284. doi: 10.1080/17513758.2017.1314025. Epub 2017 Apr 20.
Clustered regularly interspaced short palindromic repeats (CRISPR), linked with CRISPR associated (Cas) genes, can confer adaptive immunity to bacteria, against bacteriophage infections. Thus from a therapeutic standpoint, CRISPR immunity increases biofilm resistance to phage therapy. Recently, however, CRISPR-Cas genes have been implicated in reducing biofilm formation in lysogenized cells. Thus CRISPR immunity can have complex effects on phage-host-lysogen interactions, particularly in a biofilm. In this contribution, we develop and analyse a series of dynamical systems to elucidate and disentangle these interactions. Two competition models are used to study the effects of lysogens (first model) and CRISPR-immune bacteria (second model) in the biofilm. In the third model, the effect of delivering lysogens to a CRISPR-immune biofilm is investigated. Using standard analyses of equilibria, stability and bifurcations, our models predict that lysogens may be able to displace CRISPR-immune bacteria in a biofilm, and thus suggest strategies to eliminate phage-resistant biofilms.
成簇规律间隔短回文重复序列（CRISPR）与CRISPR相关（Cas）基因相连，可赋予细菌针对噬菌体感染的适应性免疫。因此，从治疗角度来看，CRISPR免疫增强了生物膜对噬菌体治疗的抗性。然而，最近CRISPR-Cas基因被认为与减少溶源细胞中的生物膜形成有关。因此，CRISPR免疫可对噬菌体-宿主-溶源菌相互作用产生复杂影响，尤其是在生物膜中。在本论文中，我们开发并分析了一系列动力学系统，以阐明并理清这些相互作用。两个竞争模型用于研究溶源菌（第一个模型）和CRISPR免疫细菌（第二个模型）在生物膜中的作用。在第三个模型中，研究了向CRISPR免疫生物膜中引入溶源菌的效果。通过对平衡点、稳定性和分岔的标准分析，我们的模型预测溶源菌可能能够在生物膜中取代CRISPR免疫细菌，从而提出消除噬菌体抗性生物膜的策略。
