Faculty & Research
- Contact Information
- Contact Karen Bush by karbush [at] indiana [dot] edu
- By telephone: 855-1542
- By fax: 812-333-6192
- SI 102B
- Research Area
- Microbial Interactions and Pathogenesis
Ph.D., Chemistry Department, Indiana University, Bloomington, IN 1970
Postdoctoral Fellow, University of California, Santa Barbara, 1970-1971
Fellow of American Academy of Microbiology (2000)
My PhD in Biochemistry was directed by Professors Henry Mahler and V. J. Shiner from the Indiana University Chemistry Department, where I studied deuterium isotope effects on the mechanism of action of the zinc-containing alcohol dehydrogenase. Following postdoctoral work, I joined the Squibb Institute for Medical Research in New Jersey where I began studying beta-lactamases, the enzymes in pathogenic bacteria that are the major cause for resistance to penicillins and other beta-lactam antibiotics. My enzymatic studies as a graduate student led to further explorations of the pharmaceutically relevant metalloenzymes, angiotensin-converting enzyme and metallo-beta-lactamases, as I tried to identify novel inhibitors of these enzymes. During my time in the pharmaceutical industry (Squibb 1973-1991; Lederle/Wyeth 1991-1996; Johnson & Johnson, 1997-2009), I was a member of scientific teams that identified and/or developed the antibiotics aztreonam (Azactam), piperacillin-tazobactam (Zosyn), levofloxacin (Levaquin), doripenem (Doribax) and the anti-MRSA cephalosporin ceftobiprole (Zeftera). My laboratory has been responsible for a number of published studies examining the mechanism of action of penicillin-binding proteins (PBPs) and various beta-lactamases that interact with these antibiotics. I have written several sets of review articles that established well-recognized beta-lactamase nomenclature, including the most highly cited article in the ASM journal Antimicrobial Agents & Chemotherapy.
As the head of the Antimicrobial Drug Discovery Research team at J&J, my work involved developing a number of high-throughput screening assays that identified novel inhibitors of bacterial enzyme targets, including the bacterial cell wall synthesizing enzymes MurA and MurF. We worked closely with a medicinal chemistry team to discover new ketolides and novel topoisomerase inhibitors with antibacterial activity against resistant gram-positive pathogens.
Current research: My laboratory is particularly known for characterizing new beta-lactamases and their interactions with various beta-lactam antibiotics. I serve as the co-gatekeeper (with George Jacoby) of the website that monitors beta-lactamase nomenclature. I am currently collaborating with several groups to determine substrate and inhibition profiles and mechanisms of resistance for new b-lactamases from resistant clinical isolates.
- Bush, K. and G. A. Jacoby. 2010. An updated functional classification of b-lactamases. Antimicrob. Agents Chemother. 54:969-976
- Queenan, A. M., W. Shang, R. Flamm, and K. Bush. 2010. Hydrolysis and inhibition profiles of b-lactamases from molecular classes A to D with doripenem, imipenem and meropenem. Antimicrob. Agents Chemother. 54: 565-569.
- Baum, E. Z., S. M. Crespo-Carbone, B. D. Foleno, L. D. Simon, J. Guillemont, M. Macielag and K. Bush. 2009. MurF inhibitors with antibacterial activity: effect on muropeptide levels. Antimicrob. Agents Chemother. 53:3240-3247.
- Baum, E. Z., S. M. Crespo-Carbone, B. J. Morrow, T. A. Davies, B. D. Foleno, W. He, A. M. Queenan and K. Bush. 2009. Effect of MexXY overexpression on ceftobiprole susceptibility in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 53:2785-2790.
- Amsler, K. M., T. A. Davies, W. Shang, M. R. Jacobs, and K. Bush. 2008. In vitro activity of ceftobiprole against pathogens from two phase 3 complicated skin and skin structure infection clinical trials. Antimicrob. Agents Chemother. 52: 3418-3423.
- Queenan, A. M. and K. Bush. 2007. Carbapenemases: the versatile beta-lactamases. Clin. Microbiol. Rev. 20:440-458.
- Davies, T.A., M. G. P. Page, W. Shang, M. Kania, and K. Bush. 2007. Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae. Antimicrob. Agents Chemother. 51: 2621-2624.
- Tennakoon, M.A., T. C. Henninger, D. Abbanat, B. D. Foleno, J. J. Hilliard, K. Bush, and M. J. Macielag. 2006. Synthesis and antibacterial activity of C6-carbazate ketolides. Bioorg. Med. Chem. Lttr. 16:6231-6235.
- Robicsek A., J. Strahilevitz,. G. A. Jacoby, M. Macielag, D. Abbanat, C. H. Park, K. Bush, and D. C.. Hooper. 2006. Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nature Med. 12:83-88.
- Bush, K., G. A. Jacoby and A. A. Medeiros. 1995. A functional classification scheme for beta-lactamases. Antimicrob. Agents Chemother. 39:1211-1233.