Dual Quorum Quenching Capsules: Disrupting two bacterial communication pathways that lead to virulence

dc.contributor.advisorBentley, William Een_US
dc.contributor.authorRhoads, Melissa Katherineen_US
dc.contributor.departmentBioengineeringen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2016-09-08T05:38:32Z
dc.date.available2016-09-08T05:38:32Z
dc.date.issued2016en_US
dc.description.abstractHealthcare Associated Infections (HAIs) in the United States, are estimated to cost nearly $10 billion annually. And, while device-related infections have decreased, the 60% attributed to pneumonia, gastrointestinal pathogens and surgical site infections (SSIs) remain prevalent. Furthermore, these are often complicated by antibacterial resistance that ultimately cause 2 million illnesses and 23,000 deaths in the US annually. Antibacterial resistance is an issue increasing in severity as existing antibiotics are losing effectiveness, and fewer new antibiotics are being developed. As a result, new methods of combating bacterial virulence are required. Modulating communications of bacteria can alter phenotype, such as biofilm formation and toxin production. Disrupting these communications provides a means of controlling virulence without directly interacting with the bacteria of interest, a strategy contrary to traditional antibiotics. Inter- and intra-species bacterial communication is commonly called quorum sensing because the communication molecules have been linked to phenotypic changes based on bacterial population dynamics. By disrupting the communication, a method called ‘quorum quenching’, bacterial phenotype can be altered. Virulence of bacteria is both population and species dependent; each species will secrete different toxic molecules, and total population will affect bacterial phenotype9. Here, the kinase LsrK and lactonase SsoPox were combined to simultaneously disrupt two different communication pathways with direct ties to virulence leading to SSIs, gastrointestinal infection and pneumonia. To deliver these enzymes for site-specific virulence prevention, two naturally occurring polymers were used, chitosan and alginate. Chitosan, from crustacean shells, and alginate, from seaweed, are frequently studied due to their biocompatibility, availability, self-assembly and biodegrading properties and have already been verified in vivo for wound-dressing. In this work, a novel functionalized capsule of quorum quenching enzymes and biocompatible polymers was constructed and demonstrated to have dual-quenching capability. This combination of immobilized enzymes has the potential for preventing biofilm formation and reducing bacterial toxicity in a wide variety of medical and non-medical applications.en_US
dc.identifierhttps://doi.org/10.13016/M2Q80X
dc.identifier.urihttp://hdl.handle.net/1903/18745
dc.language.isoenen_US
dc.subject.pqcontrolledEngineeringen_US
dc.subject.pqcontrolledMolecular biologyen_US
dc.subject.pqcontrolledBiochemistryen_US
dc.subject.pquncontrolledAI-1en_US
dc.subject.pquncontrolledAI-2en_US
dc.subject.pquncontrolledbacterial communicationen_US
dc.subject.pquncontrolledbiomaterialsen_US
dc.subject.pquncontrolledkinaseen_US
dc.subject.pquncontrolledlactonaseen_US
dc.titleDual Quorum Quenching Capsules: Disrupting two bacterial communication pathways that lead to virulenceen_US
dc.typeDissertationen_US

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