Study of 5’-methylthio-adenosine/S-adenosylhomocysteine nucleosidase (MTN) in Borrelia burgdorferi as a Drug Target

Undergraduate #149
Discipline: Chemistry and Chemical Sciences
Subcategory: Biochemistry (not Cell and Molecular Biology and Genetics)

Jesus Gonzalez - Boise State University

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Lyme disease is a tick-transmitted illness caused by the spirochaete bacteria Borrelia burgdorferi. If left untreated, Lyme disease can lead to serious health problems with symptoms such as fever, flu like headaches and inflammation of joint tissue. According to the CDC, over 30,000 cases of Lyme disease were reported in the United States in 2014. Current treatments for Lyme disease include therapeutic drugs such as doxycycline, amoxicillin and cefuroxime axetil. Though these medications prove to be effective, symptoms can persist in some patients leading to Post Treatment Lyme Disease Syndrome. This makes development of new novel antibiotics vital. 5’-methylthioadenosine/S-adenosylhomocysteine is a key component in the methionine salvage pathway and an essential part of Borrelia burgdorferi metabolic activity. In this study, a series of compounds that have shown a potential to bind in the enzyme active site and inhibit enzymatic activity were screened against recombinant Borrelia MTN. In the past, inhibitors have shown potent inhibition activity with Ki values reported in the nanomolar range, confirming MTN as an excellent drug target in the bacteria Borrelia. Future work includes inhibition assays on newly synthesized potential enzyme inhibitors referred to as the HD series. Further studies will allow for a potential determination in newly effective antibiotics.

Funder Acknowledgement(s): Ken Cornell

Faculty Advisor: Ken Cornell, kencornell@u.boisestate.edu

Role: I performed the purification of recombinant MTN. I am currently running enzymatic assays on new antibiotics in order to confirm enzymatic inhibition.