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Description
The discovery and development of novel antibacterial agents is essential to address the rising health concern over antibiotic resistant bacteria. This research investigated the antibacterial activity of a natural clay deposit near Crater Lake, Oregon, that is effective at killing antibiotic resistant human pathogens. The primary rock types in the deposit are andesitic pyroclastic materials, which have been hydrothermally altered into argillic clay zones. High-sulfidation (acidic) alteration produced clay zones with elevated pyrite (18%), illite-smectite (I-S) (70% illite), elemental sulfur, kaolinite and carbonates. Low-sulfidation alteration at neutral pH generated clay zones with lower pyrite concentrations pyrite (4-6%), the mixed-layered I-S clay rectorite (R1, I-S) and quartz.
Antibacterial susceptibility testing reveals that hydrated clays containing pyrite and I-S are effective at killing (100%) of the model pathogens tested (E. coli and S. epidermidis) when pH (< 4.2) and Eh (> 450 mV) promote pyrite oxidation and mineral dissolution, releasing > 1 mM concentrations of Fe2+, Fe3+ and Al3+. However, certain oxidized clay zones containing no pyrite still inhibited bacterial growth. These clays buffered solutions to low pH (< 4.7) and oxidizing Eh (> 400 mV) conditions, releasing lower amounts (< 1 mM) of Fe and Al. The presence of carbonate in the clays eliminated antibacterial activity due to increases in pH, which lower pyrite oxidation and mineral dissolution rates.
The antibacterial mechanism of these natural clays was explored using metal toxicity and genetic assays, along with advanced bioimaging techniques. Antibacterial clays provide a continuous reservoir of Fe2+, Fe3+ and Al3+ that synergistically attack pathogens while generating hydrogen peroxide (H2O¬2). Results show that dissolved Fe2+ and Al3+ are adsorbed to bacterial envelopes, causing protein misfolding and oxidation in the outer membrane. Only Fe2+ is taken up by the cells, generating oxidative stress that damages DNA and proteins. Excess Fe2+ oxidizes inside the cell and precipitates Fe3+-oxides, marking the sites of hydroxyl radical (•OH) generation. Recognition of this novel geochemical antibacterial process should inform designs of new mineral based antibacterial agents and could provide a new economic industry for such clays.
Antibacterial susceptibility testing reveals that hydrated clays containing pyrite and I-S are effective at killing (100%) of the model pathogens tested (E. coli and S. epidermidis) when pH (< 4.2) and Eh (> 450 mV) promote pyrite oxidation and mineral dissolution, releasing > 1 mM concentrations of Fe2+, Fe3+ and Al3+. However, certain oxidized clay zones containing no pyrite still inhibited bacterial growth. These clays buffered solutions to low pH (< 4.7) and oxidizing Eh (> 400 mV) conditions, releasing lower amounts (< 1 mM) of Fe and Al. The presence of carbonate in the clays eliminated antibacterial activity due to increases in pH, which lower pyrite oxidation and mineral dissolution rates.
The antibacterial mechanism of these natural clays was explored using metal toxicity and genetic assays, along with advanced bioimaging techniques. Antibacterial clays provide a continuous reservoir of Fe2+, Fe3+ and Al3+ that synergistically attack pathogens while generating hydrogen peroxide (H2O¬2). Results show that dissolved Fe2+ and Al3+ are adsorbed to bacterial envelopes, causing protein misfolding and oxidation in the outer membrane. Only Fe2+ is taken up by the cells, generating oxidative stress that damages DNA and proteins. Excess Fe2+ oxidizes inside the cell and precipitates Fe3+-oxides, marking the sites of hydroxyl radical (•OH) generation. Recognition of this novel geochemical antibacterial process should inform designs of new mineral based antibacterial agents and could provide a new economic industry for such clays.
ContributorsMorrison, Keith D (Author) / Williams, Lynda B (Thesis advisor) / Williams, Stanley N (Thesis advisor) / Misra, Rajeev (Committee member) / Shock, Everett (Committee member) / Anbar, Ariel (Committee member) / Arizona State University (Publisher)
Created2015
Description
Sexually transmitted diseases like gonorrhea and chlamydia, standardly treated with antibiotics, produce over 1.2 million cases annually in the emergency department (Jenkins et al., 2013). To determine a need for antibiotics, hospital labs utilize bacterial cultures to isolate and identify possible pathogens. Unfortunately, this technique can take up to 72 hours, leading to several physicians presumptively treating patients based solely on history and physical presentation. With vague standards for diagnosis and a high percentage of asymptomatic carriers, several patients undergo two scenarios; over- or under-treatment. These two scenarios can lead to consequences like unnecessary exposure to antibiotics and development of secondary conditions (for example: pelvic inflammatory disease, infertility, etc.). This presents a need for a laboratory technique that can provide reliable results in an efficient matter. The viability of DNA-based chip targeted for C. trachomatis, N. gonorrhoeae, and other pathogens of interest were evaluated. The DNA-based chip presented several advantages as it can be easily integrated as a routine test given the process is already well-known, is customizable and able to target multiple pathogens within a single test and has the potential to return results within a few hours as opposed to days. As such, implementation of a DNA-based chip as a diagnostic tool is a timely and potentially impactful investigation.
ContributorsCharoenmins, Patherica (Author) / Penton, Christopher (Thesis director) / Moore, Marianne (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Each year the hospitals in the United States dispose of viable medications worth millions of dollars. These facilities are currently forced to do so not because the medications have expired, or are no longer effective, but rather because to re-use any leftover medications would allow for the possibility of spreading disease. Once a medications sterile seal has been broken, any remaining contents of its container are considered potential pathogenic biohazards, and must be disposed of. The main objective of this thesis was to explore a potential alternative to simply discarding these lifesaving and often expensive leftover medications. The ultimate goal of this work is to establish a process by which excess drugs could be safely and effectively purified for re-use, subsequently cutting costs, and enhancing medication availability. Pseudomonas aeruginosa (P.a.) and Staphylococcus aureus (S.a) were cultured for their commonality in healthcare-associated infections (HAI's), and allowed to contaminate medication-like compounds. These bacterially inoculated solutions were meant to mimic the contaminated medications mentioned above and were then treated with a novel, physical means of pathogen inactivation named SElective PHOtonic DISinfection (SEPHODIS). Pathogen load reduction was determined through plate count assays both before and after exposure to the SEPHODIS system. structural preservation of medication was established through the use of infrared spectroscopy. The results of these experiments furthered the confidence of SEPHODIS as an efficient means of pathogen inactivation, while promoting promise of a real-world application in the form of medication purification.
ContributorsKutemeier, Hayden (Author) / Bean, Heather (Thesis director) / Tsen, Kong-Thon (Committee member) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Leprosy and tuberculosis are age-old diseases that have tormented mankind and left behind a legacy of fear, mutilation, and social stigmatization. Today, leprosy is considered a Neglected Tropical Disease due to its high prevalence in developing countries, while tuberculosis is highly endemic in developing countries and rapidly re-emerging in several developed countries. In order to eradicate these diseases effectively, it is necessary to understand how they first originated in humans and whether they are prevalent in nonhuman hosts which can serve as a source of zoonotic transmission. This dissertation uses a phylogenomics approach to elucidate the evolutionary histories of the pathogens that cause leprosy and tuberculosis, Mycobacterium leprae and the M. tuberculosis complex, respectively, through three related studies. In the first study, genomes of M. leprae strains that infect nonhuman primates were sequenced and compared to human M. leprae strains to determine their genetic relationships. This study assesses whether nonhuman primates serve as a reservoir for M. leprae and whether there is potential for transmission of M. leprae between humans and nonhuman primates. In the second study, the genome of M. lepraemurium (which causes leprosy in mice, rats, and cats) was sequenced to clarify its genetic relationship to M. leprae and other mycobacterial species. This study is the first to sequence the M. lepraemurium genome and also describes genes that may be important for virulence in this pathogen. In the third study, an ancient DNA approach was used to recover M. tuberculosis genomes from human skeletal remains from the North American archaeological record. This study informs us about the types of M. tuberculosis strains present in post-contact era North America. Overall, this dissertation informs us about the evolutionary histories of these pathogens and their prevalence in nonhuman hosts, which is not only important in an anthropological context but also has significant implications for disease eradication and wildlife conservation.
ContributorsHonap, Tanvi Prasad (Author) / Stone, Anne C (Thesis advisor) / Rosenberg, Michael S. (Thesis advisor) / Clark-Curtiss, Josephine E (Committee member) / Krause, Johannes (Committee member) / Arizona State University (Publisher)
Created2017
Description
In a series of experiments during mid 1930s, a team of researchers in New York helped establish that bacteria of the species Toxoplasma gondii can infect humans, and in infants can cause toxoplasmosis, a disease that inflames brains, lungs, and hearts, and that can organisms that have it. The team included Abner Wolf, David Cowen, and Beryl Paige. They published the results of their experiment in Human Toxoplasmosis: Occurrence in Infants as an Encephalomyelitis Verification of Transmission to Animals. Toxoplasmosis is an infection that causes inflammations in the brain (encephalitis), heart (myocarditis), and lungs (pneumonitis). The disease is caused in organisms that consume items contaminated by the protozoan parasite Toxoplasma gondii. The bacteria can transfer from pregnant women to their fetuses during pregnancy (congenitally), and it can lead those fetuses to develop physical deformities and mental disabilities. The 1930s experiments established Toxoplasma gondii as a human pathogen and helped increase research into congenital toxoplasmosis, enabling later researchers to develop measures to prevent against the disease in pregnant women.
ContributorsPotestas, Jesse (Author) / Bartlett, Zane N. (Editor) / Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo Project Encyclopedia. (Publisher) / Arizona Board of Regents (Publisher)
Created2015-06-11
Description
Water is a scarce resource that is recycled through wastewater treatment plants (WWTPs) to help fulfill the demand for water. Agriculture is a large consumer of water, indicating that WWTP-treated water is proportionally applied to crops at a high rate. Recycled water is highly regulated but is capable of containing high-risk pathogens and contaminants despite the efforts of physical and microbial treatments throughout the WWTP process. WWTPs are also producers of biosolids, treated sewage sludge regulated by the EPA that can be applied in agricultural settings to act as a fertilizer. Biosolids are a useful fertilizer as they are rich in nitrogen and contain many beneficial nutrients for soil and crops. Due to biosolids being a by-product of recycled water, they are susceptible to containing the same pathogens and contaminants that can be transferred in the WWTP systems. Antibiotic resistance (AR) is an ever-growing threat on a global scale and is one of the areas of concern for consideration of pathogen spread from WWTPs. Antibiotic resistance bacteria, created through mutation of bacterial plasmids producing antibiotic resistance genes (ARGs), have been quantified and studied to help mitigate the risk posed by continued AR spread in the environment. This study aims to produce a comprehensive collection of quantified ARG concentration data in biosolids, as well as producing a QMRA model integrating Monte Carlo distributions to provide groundwork for understanding of the direct dosage and consumption of ARGs to the standard U.S. citizen. The study determined that sul1, sul2, tetM, and tetO are ARGs of high concern in biosolid samples based on current concentration data of biosolid samples. The resulting dose models and gene concentration distributions provide data to support the need to mitigate AR risk presented by agricultural biosolid application.
ContributorsMorgan, Grace (Author) / Hamilton, Kerry (Thesis director) / Muenich, Rebecca (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2022-05