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The Battle Against

Antibiotic Resistance
Identification and Characterization of Bacterial SOS
System Inhibitors
Cindy Liao ‘17
Alex Ruberto ‘17
Charles M. Lovett, PhD.

Antibiotic Resistance: An
Overview

Trends in Microbiology 22. The Problem of Antibiotic Resistance Schäberle. & Hack. F. 165–167 (2014). M. I. T. . Overcoming the current deadlock in antibiotic research.

html .http://www.gov/drugresistance/about.cdc.

Bacterial SOS System .

H. Fifth Edition. SOS System Overview Uninduced Induced State State Lehninger Principles of Biochemistry. Freeman and Company The SOS system is induced through activation of the RecA protein. ©2008 W. .

FEMS Microbiology Reviews FEMS Microbiol Rev 31. . S. I.. J. & Barbé. Aeons of distress: an evolutionary perspective on the bacterial SOS response.SOS System Induction Erill. 637–656 (2007). Campoy.

Nature Reviews Molecular Cell Biology 11. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. 196–207 (2010).RecA Activation Moynahan. & Jasin. M. E. . M.

9901–9910 (2013). L. .LexA-RecA Interaction Kovacic. Structural insight into LexA-RecA* interaction. Nucleic Acids Research 41. et al.

Nature Chemical Biology 3. & Romesberg. A. E. . F. Combating bacteria and drug resistance by inhibiting mechanisms of persistence and adaptation. 549–556 (2007).Increased Mutagenesis Smith. P.

Increased Horizontal Gene Transfer SOS activation allows for a greater exchange of genetic information from cell-to-cell .

Our Present Study Search for compounds that inhibit SOS system induction in vitro Inhibitors can successfully stop induction through modification of RecA or LexA such that autocleavage of the LexA repressor is stopped Determine the strength of successful inhibitors in vivo Aid in the development of a drug that prevent bacteria from conferring resistance .

The Inhibitor Screening Process .

Maybridge HitFinder Collection Lipinski’s Rule of 5: ● No more than 5 hydrogen bond donors (the total number of nitrogen–hydrogen and oxygen–hydrogen bonds) ● No more than 10 hydrogen bond acceptors (all nitrogen or oxygen atoms) ● A molecular mass less than 500 daltons ● An octanol-water partition coefficient log P not greater than 5 .

Screening Process: In vitro assay .

Screening Process: In vivo assay .

Potential Inhibitors .

subtilis Compile the work from previous years and submit results to drug companies .000 compounds Obtain IC50 values for previously identified inhibitors Conduct in vivo assays on inhibitors using E.Thesis Goals Finish screening the Maybridge Library for the final 1. coli cells instead of B.

the Williams College Chemistry Department. and all the current research assistants in Lovett Lab for their assistance on this project along with all previous Lovett lab researchers for their efforts to screen the Maybridge Library. .Acknowledgements We would like to thank Professor Charles Lovett.

Questions? .