Matching Items (9)
Description
Antibiotics, bacteria, and the continuing trend of antibiotic resistance increasing in various bacteria strains is a complex and multifaceted set of relationships explored in this thesis. Examining a variety of published literature in various sectors of influence, including the social, medical, and economic divisions, this thesis examined the core factors and combined them into a set of recommendations for future progress. In this way, the subject of antibiotic resistance in bacteria begins with an evaluation of the history then continued into an analysis of the economic factors, a social understanding of the subject, a medical evaluation of current procedure, and a concluding framework and general set of recommendations for future use. Ultimately, these factors require a multifaceted approach in order to combat the numerous factors and contributions to emerging antibiotic resistance in bacteria both in the United States of America and around the world.
ContributorsMurphy, Emily Ann (Author) / Chhetri, Netra (Thesis director) / Ankeny, Casey (Committee member) / Hamburg, Robert (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Bacteria with antibiotic resistance are becoming a growing concern as the number of infections they are causing continue to increase. Many potential solutions are being researched in order to combat these pathogens. One such microbe is Pseudomonas aeruginosa, which causes acute and chronic human infections. It frequently colonizes the lungs of cystic fibrosis patients and is deadly. For these reasons, P. aeruginosa has been heavily studied in order to determine a solution to antibiotic resistance. One possible solution is the development of synbodies, which have been developed at the Biodesign Institute at Arizona State University. Synbodies are constructed from peptides that have antibacterial activity and were determined to have specificity for a target bacterium. These synbodies were tested in this study to determine whether or not some of them are able to inhibit P. aeruginosa growth. P. aeruginosa can also form multicellular communities called biofilms and these are known to cause approximately 65% of all human infections. After conducting minimum inhibitory assays, the efficacy of certain peptides and synbodies against biofilm inhibition was assessed. A recent study has shown that low concentrations of a specific peptide can cause biofilm disruption, where the biofilm structure breaks apart and the cells within it disperse into the supernatant. Taking into account this study and peptide data regarding biofilm inhibition from Dr. Aurélie Crabbé’s lab, screened peptides were tested against biofilm to see if dispersion would occur.
ContributorsPatel, Justin Hemant (Author) / Diehnelt, Chris (Thesis director) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2015-05
Description
Methicillin-Resistant Staphylococcus aureus (MRSA) infections are a major challenge to healthcare professionals. Treatment of MRSA is expensive, and otherwise avoidable deaths occur every year in the United States due to MRSA infections. Additionally, such infections lengthen patients’ stays in hospitals, keeping them out of work and adversely affecting the economy. Beta lactam antibiotics used to be highly effective against S. aureus infections, but resistance mechanisms have rendered methicillin, oxacillin, and other beta lactam antibiotics ineffective against these infections. A promising avenue for MRSA treatment lies in the use of synthetic antibodies—molecules that bind with specificity to a given compound. Synbody 14 is an example of such a synbody, and has been designed with MRSA treatment in mind. Mouse model studies have even associated Syn14 treatment with reduced weight loss and morbidity in MRSA-infected mice. In this experiment, in vitro activity of Syn 14 and oxacillin was assessed. Early experiments measured Syn 14 and oxacillin’s effectiveness in inhibiting colony growth in growth media, mouse serum, and mouse blood. Syn14 and oxacillin had limited efficacy against USA300 strain MRSA, though interestingly it was noted that Syn14 outperformed oxacillin in mouse serum and whole mouse blood, indicating the benefits of its binding properties. A second experiment measured the impact that a mix of oxacillin and Syn 14 had on colony growth, as well as the effect of adding them simultaneously or one after the other. While use of either bactericidal alone did not show a major inhibitory effect on USA300 MRSA colony growth, their use in combination showed major decreases in colony growth. Moreover, it was found that unlike other combination therapies, Syn14 and oxacillin did not require simultaneous addition to MRSA cells to achieve inhibition of cell growth. They merely required that Syn14 be added first. This result suggests Syn14’s possible utility in therapeutic settings, as the time insensitivity of synergy removes a major hurdle to clinical use—the difficulty in ensuring that two drugs reach an affected area at the same time. Syn14 remains a promising antimicrobial agent, and further study should focus on its precise mechanism of action and suitability in clinical treatment of MRSA infections.
ContributorsMichael, Alexander (Author) / Diehnelt, Chris (Thesis director) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
In 2015, the World Health Organization cited antibiotic resistance as one of the greatest current challenges to global public health. A major driver of the evolution of antibiotic resistance is the overuse and misuse of these drugs. While antibiotic stewardship, education campaigns, and health policy attempt to limit drug use globally, public understanding of antibiotic resistance and its consequences are lacking. The goal of this study is to analyze the social and cultural influences of antibiotic knowledge and usage behavior. Over a three-month period, I interviewed 211 laypersons in Guatemala, Spain, the Netherlands, India, South Africa, and New Zealand to understand their ideas, perceptions, and behaviors regarding antibiotics and compared results across countries. While an overall consensus across countries does exist, I found significant differences between low and high income countries as well as between low and high antibiotic consumption countries. Additionally, I found that having increased public health knowledge is related to lower antibiotic "risky" behavior. These results help contextualize national data on antibiotic consumption and resistance by illustrating relationships between access, beliefs, and consumption patterns within populations. The results also inform the development of community and culture specific educational campaigns regarding antibiotic resistance.
ContributorsHarris, Carlyn Larson (Author) / Maupin, Jonathan (Thesis director) / Gaughan, Monica (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Aminoglycosides contain a basic unit of an amino-modified glycoside (sugar) and have potent antibacterial properties used to treat a wide range of bacterial infections, including those that occur in the soft tissue, chest, urinary tract, and endocardial tissue.1, 2 With a broad spectrum of activity and convenient dosing schedule, Aminoglycoside helps to effectively fight off Gram-negative bacteria.1, 3 In 1944 an aminoglycoside called streptomycin entered clinical trials to test its effectiveness as an antibiotic.4 After several years other classes of aminoglycosides were discovered such as neomycin, gentamicin, kanamycin, and netilmicin.4 When introduced these antibiotics presented major clinical advancements in the treatment of Tuberculosis and other bacterial infections.3, 4 However their use in modern medicine has diminished due to their toxicity, required parenteral delivery, and the availability of alternative antibiotics.3, 5 The dose-dependent toxicity of aminoglycosides limits their use due to a narrow range of safe aminoglycoside plasma concentrations.3, 5 Exceeding this range in non-target tissues can lead to negative effects on the audio-vestibular apparatus and kidneys.3, 5, 6 In the 1980’s, clinicians began treating infections with antibiotics that were perceived as less toxic and providing broader antibacterial activity.7 This resulted in aminoglycosides being prescribed for more persistent infections that were resistant to other antibiotics.3 With the amount of antibiotic resistant bacteria increasing, many scientists have begun looking into methods for minimizing aminoglycoside toxicity and maximizing its antibacterial activity.3, 8 These methods include encapsulation and polymer conjugation.9, 10 By encapsulating aminoglycosides in liposomes or other vesicles scientists aim to increase its concentration in infected tissues while decreasing nephro- and ototoxicity.9 With conjugated polymers scientists have created polymer complexes containing aminoglycosides and other compounds such as dopamine.11 The goal of these polymers is to limit toxicity by slowing antibiotic release and increasing efficacy of the antibiotic through targeted delivery and toxicity of other compounds.9, 10, 11 Other than its use in treating infections, aminoglycosides are gaining attention as an excellent vehicle for gene delivery.12 In this application aminoglycosides are used to correct a genetic defect by introducing a normal copy of the gene into affected cells.12,13 Currently scientists are assessing aminoglycosides for gene therapy in the treatment of cancer and various other diseases.12, 14 This review will focus on the diverse customizability of aminoglycosides in treating infections and as vehicles for gene therapy.
ContributorsWampler, Cole (Author) / Rege, Kaushal (Thesis director) / Schoepf, Jared (Committee member) / Barrett, The Honors College (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Chemical Engineering Program (Contributor) / School of Life Sciences (Contributor)
Created2023-05
Description
Bdellovibrio bacteriovorus (B. bacteriovorus) is a predatory bacterium that preys on other gram-negative bacteria. In order to survive and reproduce, B. bacteriovorus invades the periplasm of other bacterial cells creating the potential for it to act as a “living antibiotic”. In this work, a comparison was made between the rates of predation of B. bacteriovorus in vitro and in vivo. In vitro, the behavior of B. bacteriovorus was examined in the presence of prey. In vivo, the behavior of B. bacteriovorus was examined in the presence of prey and a living host, Caenorhabditis elegans (C. elegans). C. elegans were infected with Escherichia coli (E. coli) and treated with B. bacteriovorus. In previous studies that analyzed B. bacteriovorus in vitro, a decrease in concentrations of bacteria has been observed after introduction of B. bacteriovorus. In vivo, B. bacteriovorus were found to not have a net reduction of E. coli but to reproducibly raise the level of fluctuations in E. coli concentrations.
ContributorsPerry, Nicole (Author) / Presse, Steve (Thesis director) / Mangone, Marco (Committee member) / Barrett, The Honors College (Contributor) / Economics Program in CLAS (Contributor) / School of Molecular Sciences (Contributor)
Created2023-05
Description
This dissertation studies the larger issue of antibiotic resistance with respect to how antibiotics are being introduced into the environment, focusing on two major anthropogenic pathways: animal husbandry for human consumption, and the recycling of wastewater and municipal sludge generated during conventional biological sewage treatment.
For animal production on land (agriculture) antibiotics are often used for growth enhancement and increased feed efficiency. For animal production in water (aquaculture) antibiotics are often used as a prophylactic. I found that the same antibiotics are being used in both industries and that the same strains of human pathogens have also been isolated from both sources, expressing identical resistance mechanisms. In U.S. seafood, five out of 47 antibiotics screened for were detected at levels of 0.3 to 7.7 ng/g fresh weight. Although compliant with FDA regulations, the risk for resistance still exists, as even low antibiotic concentrations have been shown to exert selective pressure on bacteria.
Similarly low concentrations of antibiotics were found in U.S. biosolids at levels of 0.6 to 19.1 ng/g dry weight. Of the five antibiotics detected, two have never been reported before in biosolids. Three have never been reported before in U.S. biosolids. Using the raw numbers obtained from antibiotic screenings in biosolids, I assessed the impact of employing four different LC-MS/MS methods, concluding that analysts should experimentally determine the most appropriate quantitation method based on the analyte targeted, matrix investigated, and research goals pursued. Preferred quantitation approaches included the isotope dilution method with use of an analogous standard and, although time and resource demanding, the method of standard addition.
In conclusion, antibiotics introduced into the environment via agriculture, aquaculture, and wastewater recycling pose a combination of chemical and biological threats. Aside from exerting outright chemical toxicity to non-target organisms, antibiotic residues can promote the development of multi-drug resistance in human pathogens. Public health protection approaches to stem the risks posed by animal husbandry may include reserving drugs for exclusive, human use, decreasing their usage altogether, improving reporting efforts, reevaluating existing regulations on agricultural and aquacultural antibiotic usage, and improved risk assessment for biosolids application on land.
For animal production on land (agriculture) antibiotics are often used for growth enhancement and increased feed efficiency. For animal production in water (aquaculture) antibiotics are often used as a prophylactic. I found that the same antibiotics are being used in both industries and that the same strains of human pathogens have also been isolated from both sources, expressing identical resistance mechanisms. In U.S. seafood, five out of 47 antibiotics screened for were detected at levels of 0.3 to 7.7 ng/g fresh weight. Although compliant with FDA regulations, the risk for resistance still exists, as even low antibiotic concentrations have been shown to exert selective pressure on bacteria.
Similarly low concentrations of antibiotics were found in U.S. biosolids at levels of 0.6 to 19.1 ng/g dry weight. Of the five antibiotics detected, two have never been reported before in biosolids. Three have never been reported before in U.S. biosolids. Using the raw numbers obtained from antibiotic screenings in biosolids, I assessed the impact of employing four different LC-MS/MS methods, concluding that analysts should experimentally determine the most appropriate quantitation method based on the analyte targeted, matrix investigated, and research goals pursued. Preferred quantitation approaches included the isotope dilution method with use of an analogous standard and, although time and resource demanding, the method of standard addition.
In conclusion, antibiotics introduced into the environment via agriculture, aquaculture, and wastewater recycling pose a combination of chemical and biological threats. Aside from exerting outright chemical toxicity to non-target organisms, antibiotic residues can promote the development of multi-drug resistance in human pathogens. Public health protection approaches to stem the risks posed by animal husbandry may include reserving drugs for exclusive, human use, decreasing their usage altogether, improving reporting efforts, reevaluating existing regulations on agricultural and aquacultural antibiotic usage, and improved risk assessment for biosolids application on land.
ContributorsDone, Hansa Yi-Yun (Author) / Halden, Rolf U. (Thesis advisor) / Haydel, Shelley E (Committee member) / Abbaszadegan, Morteza (Committee member) / Arizona State University (Publisher)
Created2015
Eradication of multidrug-resistant bacteria using biomolecule-encapsulated two-dimensional materials
Description
The increasing pervasiveness of infections caused by multidrug-resistant bacteria (MDR) is a major global health issue that has been further exacerbated by the dearth of antibiotics developed over the past 40 years. Drug-resistant bacteria have led to significant morbidity and mortality, and ever-increasing antibiotic resistance threatens to reverse many of the medical advances enabled by antibiotics over the last 40 years. The traditional strategy for combating these superbugs involves the development of new antibiotics. Yet, only two new classes of antibiotics have been introduced to the clinic over the past two decades, and both failed to combat broad spectrum gram-negative bacteria. This situation demands alternative strategies to combat drug-resistant superbugs. Herein, these dissertation reports the development of potent antibacterials based on biomolecule-encapsulated two-dimensional inorganic materials, which combat multidrug-resistant bacteria using alternative mechanisms of strong physical interactions with bacterial cell membrane. These systems successfully eliminate all members of the ‘Superbugs’ set of pathogenic bacteria, which are known for developing antibiotic resistance, providing an alternative to the limited ‘one bug-one drug’ approach that is conventionally used. Furthermore, these systems demonstrate a multimodal antibacterial killing mechanism that induces outer membrane destabilization, unregulated ion movement across the membranes, induction of oxidative stress, and finally apoptotic-like cell death. In addition, a peptide-encapsulation of the two-dimensional material successfully eliminated biofilms and persisters at micromolar concentrations. Overall, these novel systems have great potential as next-generation antimicrobial agents for eradication of broad spectrum multidrug-resistant bacteria.
ContributorsDebnath, Abhishek (Author) / Green, Alexander A (Thesis advisor) / Liu, Yan (Committee member) / Stephanopoulos, Nicholas (Committee member) / Arizona State University (Publisher)
Created2019
Description
The aim of the present study was to review the symptoms and current treatment options of the most common skin infections seen in outpatient settings and develop a preliminary alternative treatment solution. The specific skin infections evaluated were those caused by Staphylococcus and Streptococcus bacterial species, and are frequently treated with a wide variety of systemic antibiotics or topical ointments. Systemic antibiotics have shown increased occurrence of adverse side effects as well as the development of antibiotic-resistant bacteria. Additionally, these medications are usually overprescribed, which may further exacerbate negative side effects. Another issue that is addressed is the development of infections following treatment of a new laceration or other trauma to the skin. A patient may be treated for their wound with stitches or another alternative, but there is still the possibility of developing an infection later.
This study synthesizes information found from extensive research and provides a review of the most optimal techniques for developing an alternative to systemic antibiotics. The final deliverable is a report detailing the significant findings and discussing the ways that this solution may be developed further and implemented in a clinical setting. The solution is a hydrogel bandage designed to deliver antibiotics directly to the wound site, while also offering protection and enhanced wound healing. The target population is patients suffering from skin conditions in an outpatient setting. The antibiotics of interest for this solution are clindamycin, doxycycline, and trimethoprim-sulfamethoxazole (co-trimoxazole), as they offer excellent treatment against gram-positive bacteria and methicillin-resistant Staphylococcus aureus. However, other broad-spectrum antibiotics could potentially be incorporated to protect against gram-negative bacteria. The design features a polyvinyl alcohol (PVA) hydrogel that has shown many properties that are beneficial to biomedical applications, including biocompatibility, flexibility, high drug-loading capacity, high absorption of wound exudate, increased promotion of wound healing, and more. Preliminary mathematical models of the hydrogel’s drug delivery behaviors are also included. Due to the scope and timeframe of this project, the majority of findings herein are based on research of prior literature instead of development of the novel device. Future directions would include further research and development of the mechanisms behind the device, creation of a physical prototype, experimental testing, and statistical analyses to verify device specifications and capabilities.
This study synthesizes information found from extensive research and provides a review of the most optimal techniques for developing an alternative to systemic antibiotics. The final deliverable is a report detailing the significant findings and discussing the ways that this solution may be developed further and implemented in a clinical setting. The solution is a hydrogel bandage designed to deliver antibiotics directly to the wound site, while also offering protection and enhanced wound healing. The target population is patients suffering from skin conditions in an outpatient setting. The antibiotics of interest for this solution are clindamycin, doxycycline, and trimethoprim-sulfamethoxazole (co-trimoxazole), as they offer excellent treatment against gram-positive bacteria and methicillin-resistant Staphylococcus aureus. However, other broad-spectrum antibiotics could potentially be incorporated to protect against gram-negative bacteria. The design features a polyvinyl alcohol (PVA) hydrogel that has shown many properties that are beneficial to biomedical applications, including biocompatibility, flexibility, high drug-loading capacity, high absorption of wound exudate, increased promotion of wound healing, and more. Preliminary mathematical models of the hydrogel’s drug delivery behaviors are also included. Due to the scope and timeframe of this project, the majority of findings herein are based on research of prior literature instead of development of the novel device. Future directions would include further research and development of the mechanisms behind the device, creation of a physical prototype, experimental testing, and statistical analyses to verify device specifications and capabilities.
ContributorsTanner, Emily Christine (Author) / Pizziconi, Vincent (Thesis director) / Nguyen, Eric (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05