Unexpected Antibiotic Resistance in Gram-Positive Bacteria Recovered from the Chesapeake Bay and Associated Rivers and Investigating the Antimicrobial Activity of a Wide Variety of Essential Oils as a Means to Identify Novel Drug Targets

Antibiotic Resistance;Essential Oils;Chesapeake Bay;not listed

Rivers, Jennifer LeighParrish, Nicole M. ;

Johns Hopkins University

关键词: Antibiotic Resistance;    Essential Oils;    Chesapeake Bay;    not listed;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/39480/RIVERS-THESIS-2016.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Drug resistant bacterial infections pose a serious hurdle to effective healthcare today. Multi-drug resistant infections are becoming more widespread which further complicates patient care. If a bacterium develops resistance to one antimicrobial, it is far more likely to develop resistance to other drugs (Gould, 2008). In patients with drug resistant infections, morbidity, mortality and hospital costs virtually double compared to patients with susceptible organisms (French, 2010; Gould, 2009; Livermore, 2007). The emergence and spread of antibiotic resistance is a complex issue with many contributing factors, including frequent antibiotic exposure, antibiotic use in industrial agriculture, ease of international travel, current antibiotic prescribing practices, and less than optimal infection control and hygiene.To better understand the origins and emergence of antibiotic resistance in clinical pathogens, bacteria in the environment must be considered to elucidate transmission of resistance determinants between genera and species. For example, plasmid-mediated, fluoroquinolone resistance is suspected to have originated in aquatic bacteria living in polluted water systems. However, the fluoroquinolones are not the only class of antibiotics for which resistance has emerged in an environmental setting. Some resistance to aminoglycosides, via a methylase enzyme, is hypothesized to have originated in environmental Actinomycetes known to produce this class of drugs. Combined with exposure through industrial agriculture, it is easy to see how resistance to aminoglycosides could be facilitated leading to more widespread dissemination in the environment (Gould, 2008). Additionally, extended spectrum β-lactamase (ESBLs) enzymes, now a major hurdle in the treatment of Gram-negative bacterial infections, originated in Kluyvera species, a genus of environmental bacteria of little clinical importance (Pfeifer, 2010; Livermore, 2006). Yet, the transfer of ESBLs is so widespread now, that nearly all β-lactam antibiotics are affected, hindering our ability to treat serious Gram-negative infections.These are merely a few examples of the environment acting as a reservoir for potentially disastrous, transferable resistance determinants. It has been well established that clinically important human pathogens can acquire novel resistance from environmental bacteria (French, 2010). If we hope to further our understanding of the emergence of antibiotic resistance and prevent future development of resistance, the complicity of the environment should not be overlooked or underestimated.In addition to preventing further spread of antimicrobial resistance, new drugs are sorely needed, both to help in fighting antibiotic resistant infections that continue to occur, but also to help reduce the selection pressure caused by frequent use of the same antibiotics time and time again. With antibiotic development currently at a stand-still, new approaches are desperately needed for discovery of novel agents. For this reason, we looked to the past, specifically the ancient past, for possible novel drugs and/or identification of drug targets. In antiquity, essential oils were used to combat a large number of maladies, including infections. Many historical documents as well as current studies have demonstrated the potent activity of various essential oils against a select number of bacterial pathogens. With the advent of modern techniques such as gas chromatography-mass spectrometry, we are learning about the intricate complexities of essential oils and the potent components contained in their mixtures. These components are in essence concentrated mixtures of secondary metabolites from various plant structures, including stems, flowers, leaves, and seeds. The function of these mixtures, from the plant’s point of view, are for protection from bacterial, fungal, and viral pathogens. Thus, due to the sheer variety of bacteria in the environment and the multitude of plants already producing antimicrobial compounds, it is likely that novel antimicrobials with unique mechanisms of action have yet to be discovered. By studying the antimicrobial activity of a large number of essential oils in tandem with a wide range of bacteria and fungi, it may be possible to discern patterns of oil-organism specific activity indicative of a unique mechanism of action. To the best of our knowledge, this thesis represents the first study of its type in which over 80, highly purified essential oils have been tested against a wide array of both susceptible and multi-drug resistant Gram-positive and Gram-negative bacteria and fungi of clinical importance.