Grand Valley State University, Biology, Allendale, MI 49401
Increasing resistance to antibiotics by certain bacterial species has made it imperative that novel compounds be tested and used to help alleviate the rise of resistance to penicillin-based antibiotics. The main focus of our research is to test a known telomerase inhibitor for potential antimicrobial activity. Telomerase catalyzes the elongation of the telomeres, the ends of eukaryotic chromosomes. The enzyme is a ribonucleoprotein, which acts as a reverse transcriptase, and has been associated with unlimited proliferation in cancer cells; as such, telomerase has been targeted by novel drugs to treat cancer. One of these inhibitors, BIBR1532 {(E)-2-(3-(naphthalene-2-yl)but-2enamido)benzoic acid, is currently in clinical trials, and is being tested as a non-competitive inhibitor of telomerase. To examine the antimicrobial properties of BIBR1532, crystals were dissolved in sterile 20% triethanolanime, for a final concentration of 10mg/ml. Disk Diffusion tests, along with tests for the minimum inhibitory concentration (MIC) when appropriate, were preformed on the following organisms: Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, Klebsiella pneumoniae, Micrococcus leuteus, Proteus vulgaris, Aspergillus fumigatus, Candida albicans, Candida parapsilosis, Candida krusei, Candida glabrata and Mycobacterium smegmatis. BIBR1532 only showed inhibition against S. aureus, S. pneumoniae, M. leuteus, B. subtilis, S. epidermidis, and M. smegmatis. Initial tests for the MIC of BIBR1532 have shown it to range from 0.157mg/ml-0.63 mg/ml. Presently, no known testing of BIBR1532 against bacteria has been performed or published. Since BIBR1532 inhibited the growth of normal S. aureus, it is likely that it will inhibit MRSA; thus this compound will be tested on MRSA. Additionally, chemically synthesized derivatives of BIBR1532 will also be tested for inhibition properties. Our results demonstrate that it is worthwhile to continue the search for novel antibiotics. These compounds can be found in nature, or as in our case, synthetic antibiotics can already exist.
A.J. Walker was supported by a Student Summer Scholars (S3) grant, College of Interdisciplinary Studies, Grand Valley State University.
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