Title Information
Title
Enhanced Efficacy of Nanotechnology-Driven Approaches against Antibiotic-Resistant Biofilms in the Presence of Metabolites
Name: Personal
Name Part
Durmus, Naside Gozde
Role
Role Term: Text
creator
Origin Information
Copyright Date
2013
Physical Description
Extent
36, 191 p.
digitalOrigin
born digital
Note
Thesis (Ph.D. -- Brown University (2013)
Name: Personal
Name Part
Webster, Thomas
Role
Role Term: Text
Director
Name: Personal
Name Part
Webster, Thomas
Role
Role Term: Text
Reader
Name: Personal
Name Part
Tripathi, Anubhav
Role
Role Term: Text
Reader
Name: Personal
Name Part
Sun, Shouheng
Role
Role Term: Text
Reader
Name: Personal
Name Part
Morgan, Jeffrey
Role
Role Term: Text
Reader
Name: Personal
Name Part
Tripathi, Anubhav
Role
Role Term: Text
Director
Name: Corporate
Name Part
Brown University. Biomedical Engineering
Role
Role Term: Text
sponsor
Genre (aat)
theses
Abstract
Antibiotic resistance and the lack of new antimicrobial therapies create significant challenges for the treatment of infections. Therefore, there is an urgent clinical need to develop novel treatments targeting bacterial biofilms to reduce the risk of infection, without resorting to antibiotics. The goal of this thesis is, for the first time, to integrate two novel approaches, i.e. nanotechnology and metabolic stimulation, to eradicate antibiotic-resistant biofilms. The metabolic microenvironment of the biofilms has been manipulated to improve the antibacterial properties of superparamagnetic iron oxide nanoparticles (SPION) as well as nanorough device surfaces. First, it has been shown that engineered nanoscale topographies provide surfaces that are more resistant to bacterial growth than conventional polyvinyl chloride (PVC). In addition, for the first time, the presence of fructose on the nanorough PVC further decreased the planktonic S. aureus growth and biofilm formation, without use of any antibiotics. Moreover, a simple, broad-spectrum and low-cost dual-sided approach which uses SPION in combination with metabolites (i.e., fructose, glucose, and mannitol) has been developed as an alternative to existing antibacterial strategies. This strategy offers further improved efficacy of SPION against persistent gram-positive and gram-negative bacteria infections by manipulating the biofilm metabolic microenvironment, creating a new nanotechnology-driven approach. Further, biofilm eradication by the engineered SPION was significantly better than vancomycin, the antibiotic of last resort. In addition, it has been demonstrated that SPION conjugated with antibacterial silver salts exhibit strong eradication properties against the antibiotic-resistant (MRSA) biofilms. Antibacterial properties of silver-conjugated SPION were further improved when an external magnetic field was applied as their magnetic core enabled them to penetrate into the biofilms. This thesis, for the first time, highlighted the importance of biofilm metabolic microenvironment for the nanotechnology-driven approaches. It is envisioned that these simple and inexpensive approaches could lead to novel alternative treatments to the only current clinical option, vancomycin, which MRSA has started to develop a resistance towards. These novel nanotechnology-driven approaches can lead to successful clinical outcomes in terms of minimizing infections, longer medical device lifetimes, and decreasing antibiotic usage.
Subject
Topic
antibiotic resistance
Subject
Topic
antibacterial
Subject
Topic
metabolic simulation
Subject
Topic
superparamagnetic iron oxide nanoparticles (SPION)
Subject
Topic
nanorough surface
Subject (FAST) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/1032639")
Topic
Nanotechnology
Subject (FAST) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/810407")
Topic
Antibacterial agents
Subject (FAST) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/832066")
Topic
Biofilms
Record Information
Record Content Source (marcorg)
RPB
Record Creation Date (encoding="iso8601")
20131219
Language
Language Term: Code (ISO639-2B)
eng
Language Term: Text
English
Identifier: DOI
10.7301/Z03R0R6C
Access Condition: rights statement (href="http://rightsstatements.org/vocab/InC/1.0/")
In Copyright
Access Condition: restriction on access
Collection is open for research.
Type of Resource (primo)
dissertations