Nanomaterials for controlling bacterial pathogens and resistance occurrence
lnfectious diseases are the leading cause of death worldwide while the constantly raising antimicrobial resistance (AMR) is a major concern for the public health. During the infection establishment bacteria! pathogens communicate via expression of signaling molecules, controlled through a phenomenon...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/673983 |
| Acceso en línea: | http://hdl.handle.net/10803/673983 https://dx.doi.org/10.5821/dissertation-2117-365524 |
| Access Level: | acceso abierto |
| Palabra clave: | Àrees temàtiques de la UPC::Enginyeria química 66 |
| Sumario: | lnfectious diseases are the leading cause of death worldwide while the constantly raising antimicrobial resistance (AMR) is a major concern for the public health. During the infection establishment bacteria! pathogens communicate via expression of signaling molecules, controlled through a phenomenon called quorum sensing (QS). As a result of this, bacteria produce virulence factors and form resistant biofilms on living and non-living surfaces causing persistent infections. The infection complexity, especially in chronic diseases, requires the use of broad-spectrum antibiotics responsive for the appearance and the spread of drug resistant species. lnfections caused by antibiotic-resistant pathogens are associated with high morbidity, mortality, and huge economic burden. Unlike the decrease over the past three decades of the number of novel marketed antimicrobial drugs, the number of antibiotic resistant bacteria! strains steadily increases. Thus, there is an urgent need for development of alternative strategies to manage difficult-to-treat infections. This thesis aims at the engineering of advanced nano-enabled materials and nanostructured coatings for controlling bacteria! pathogenesis and resistance occurrence. To achieve this, biopolymers, antibiofilm and anti-infective enzymes. and inorganic compounds were nano-hybridized as altemative modalities to the conventional antibiotics. The nanoform was able to provide enhanced interaction with bacteria! cell membranes and easier penetration into biofilms, increasing the antimicrobial efficacy at lower dosages, while preventing from development of antimicrobial resistance. Additionally, specific targeting moieties increased the nanomaterial's interaction with the pathogens, avoiding the drug resistance appearance and cytotoxicity. The first part ofthe thesis describes the functionalization of biologically inert nanoparticles (NPs) with membrane disturbing antimicrobial aminocellulose (AM) and biocompatible hyaluronic acid (HA) in an Lbl fashion for elimination of medically relevant pathogens. The generated nanoentities demonstrated high potential to inhibit the biofilm formation, without affecting the human cell viability. Further, the Lbl technique was applied to decorate antimicrobial, but potentially toxic silver (Ag) nano-templates with biocompatible AM and quorum quenching (QQ) acylase in order to obtain safe antibacterial and antibiofilm nanomaterials. The deposition of acylase and AM on the Ag core interfered with the QS signaling and bacteria! pathogenesis, and enhanced the NPs interaction with the bacteria! membrane. The integration of a triple mechanisms of action in the hybrid nanoentities resulted in complete bacteria and biofilm eradication and improved biocompatibility ofthe AgNPs. The thesís also describes the development of targeted nanocapsules (NCs) for selective elimination of Staphylococcus aureus. Herein, self-assembling nanoencapsulation technology using the biocompatible and biodegradable proteín zein was applied for the generation of zein NCs loaded with bactericida! oregano essential oil (EO). An antibody specifically targeting S. aureus was covalently grafted on the NCs surface. The obtained targeted NCs demonstrated antibacterial selectivity in a mixed bacteria! inoculum, and the treatment efficacy was validated in an in vitro coculture model of bacteria and mammalian cells. Finally, high intensity ultrasonochemistry (US) process was employed for engineering of durable antibacterial/antibiofilm coating on urinary catheters. The simultaneous deposition of zinc oxide (ZnO) NPs anda matrix-degrading amylase enzyme improved the NPs adhesion on the silicone material, and prevented its bacteria! colonization and biofilm formation in vitro. The hybrid nanostructured coating delayed the occurrence of early onset urinary tract infections (UTls) and showed excellent biosafety in an in vivo animal model. |
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