Molecular insights into virulence regulation in MRSA using mass-spectrometry based metabolomics

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Derick D. Jones Jr. (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: Drug resistant infections are an increasing problem world-wide, with an annual estimate of 300,000 infections a year, 10,000 deaths, and 1.7 billion dollars in costs in the US alone. Current treatment modalities to combat infections of this type rely on antibiotics. Unfortunately, the use of antibiotics accelerates the development of resistance. Severe drug resistant infections such as methicillin-resistant Staphylococcus aureus (MRSA) are often managed with “last resort treatments”, which have side effects similar to chemotherapy, including, but not limited to, loss of appetite for months at a time, increased hospital stays, and extreme fatigue. MRSA produces a host of toxins that are responsible for its virulence, causing inflammation, skin lesions and, in extreme cases, septic shock and even death. One potential alternative strategy for treating drug resistant bacterial infections would be to inhibit the production of these toxins, thereby making the bacteria less harmful to the host; a so called “anti-virulence” approach. A major advantage of anti-virulence therapeutics would be the ability to reduce the damage caused by bacterial infections without selecting for the development of resistance. The long-term goal of our research is to develop new anti-virulence strategies against MRSA. With this dissertation, we undertook three projects towards this goal. With Project 1, we developed analytical methodologies to better understand and track virulence in MRSA by measuring molecules that are regulated by and regulate the quorum sensing system. With Project 2, we sought to identify new secondary metabolites produced by MRSA, with a particular focus on those regulated by the quorum sensing system. Lastly, with Project 3, we employed new informatic approaches to identify antimicrobial compounds from the plant Rumex crispus. This third project also included a significant training component and was carried out collaboratively with an undergraduate student. A central goal of this dissertation in addition to benchwork science was to recruit and retain a diverse body of students in chemistry. This goal was carried out through effective mentorship and training, as evidenced by the outcomes of Project 3.

Additional Information

Language: English
Date: 2020
Antimicrobials, Bioinformatics, Mass-Spectrometry, Mentorship, MRSA, Quorum-Sensing
Virulence (Microbiology) $x Molecular aspects
Staphylococcus aureus infections
Methicillin resistance
Anti-infective agent

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