Inhibiting antimicrobial resistance in Staphylococcus aureus using natural products

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Keivan A. Ettefagh (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Nadja Cech

Abstract: Since the treatment of infections with antibiotics, Staphylococcus aureus has developed resistance to antimicrobial agents. Methicillin-resistant S aureus (MRSA) contributes significantly to the healthcare burden of both hospital and community infections. Investigation into the resistance mechanism and their inhibition has the potential to increase the effectiveness in treating infection. It is hypothesized that the diversity of compounds and efficacy found in complex natural product extracts would lead to active leads that inhibit bacterial resistance. Using synergistic activity testing as a guide to a fractionation process, 3 flavonoids (8-desmethyl-sideroxylin, sideroxylin, and 6-desmethyl-sideroxlyn) were identified as synergists within a Hydrastis canadensis extract. These compounds were further characterized as efflux pump inhibitors using fluorescence in real-time and under confocal microscopy. In addition to disrupting efflux, the ability of S. aureus to cause disease was investigated. By detecting auto-inducing peptide I (AIP I), a direct product in the activation of this pathway, inhibition via natural products could be determined. Disruption in the intercellular communication via the Agr quorum sensing pathway in MRSA was observed in a Penicillium fungus and in H. canadensis. This quorum sensing inhibition (quorum quenching) limits virulence and toxin production making it easier for the host to manage infection.

Additional Information

Publication
Dissertation
Language: English
Date: 2013
Keywords
Antimicrobial, Efflux Pump, MRSA, Quorum Sensing, Staphylococcus aureus, Synergy
Subjects
Methicillin resistance
Staphylococcus aureus
Drug resistance in microorganisms

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