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Indiana University Bloomington

Department of Biology

Faculty & Research

Faculty Profile

Karen Bush

Photo of Karen Bush
Professor of Practice in Biotechnology, Adjunct Professor of Biology

IU Affiliations
Biochemistry
Biotechnology

Contact Information
By telephone: 855-1542
By fax: 812-333-6192
SI 102B
Research Area
Microbial Interactions and Pathogenesis
Education

Ph.D., Chemistry Department, Indiana University, Bloomington, IN 1970
Postdoctoral Fellow, University of California, Santa Barbara, 1970-1971

Awards

Fellow of American Academy of Microbiology (2000)

ICAAC Award from ASM (2014)

Research Description

My PhD in Biochemistry from the Indiana University Chemistry Department involved the study of 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 and began studying beta-lactamases, the enzymes in pathogenic bacteria that are the major cause for resistance to penicillins and other beta-lactam antibiotics. ` During my time in the pharmaceutical industry (Squibb 1973-1991; Lederle/Wyeth 1991-1996; Johnson & Johnson, 1997-2009), my scientific teams 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 the beta-lactam antibiotics. I have authored a number of review articles that have established one of the most commonly used beta-lactamase nomenclature schemes. 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. Our lab currently collaborates with several groups to characterize beta-lactamase production from resistant clinical isolates.  Our work has served to alert hospitals in Indianapolis to the need for increased infection control to minimize the risk from carbapenem-resistant Enterobacteriaceae ("CRE"), deemed by the CDC to pose an Urgent Threat to the health care community.  My lab has also collaborated with several pharmaceutical companies to characterize investigational antibacterial agents regarding susceptibility profiles and mechanism of action as part of the information that will be shared with the FDA for possible drug approvals.

Select Publications
M. Estabrook, M. B. Bussell, S. L. Clugston and K. Bush. In vitro activity of ceftolozane-tazobactam against recent United States Escherichia coli isolates encoding CTX-M-type extended spectrum β-lactamases from 2010-2011 as determined by broth dilution and agar diffusion assays.  J. Clin. Microbiol. Accepted for publication, Aug. 17, 2014.

Hayakawa, K., S. Gattu, D. Marchaim, A. Bhargava, M. Palla, K. Alshabani, U. M. Gudur, H. Pulluru, P. Bathina, P. R. Sundaragiri, M. Sarkar, H. Kakarlapudi, B. Ramasamy, P. Nanjireddy, S. Mohin, M. Dasagi, S. Datla, V. Kuchipudi, S. Reddy, S. Shahani, V. Upputuri, S. Marrey, V. Gannamani, N. Madhanagopal, S. Annangi, B. Sudha, K. S. Muppavarapu, J. A. Moshos, P. R. Lephart, J. M. Pogue, K. Bush, and K. S. Kaye. 2013. Epidemiology and risk factors for isolation of Escherichia coli producing CTX-M-type extended-spectrum β-lactamase in a large U.S. medical center. Antimicrobial Agents & Chemotherapy 57:4010-4018.

Bush, K., M. Pannell, J. L. Lock, A. M. Queenan, J. H. Jorgensen, R. M. Lee, J. S. Lewis, and D. Jarrett.  2013.  Detection systems for carbapenemase gene identification should include the SME serine carbapenemase. Intl. J. Antimicrob. Agents 41:1-4

Bush, K., P. Courvalin, G. Dantas, J. Davies, B. Eisenstein, P. Huovinen, G. A. Jacoby, R. Kishony, B. N. Kreiswirth, E. Kutter, S. A. Lerner, S. Levy, K. Lewis, O. Lomovskaya, J. H. Miller, S. Mobashery, L. J. V. Piddock, S. Projan, C. M. Thomas, A. Tomasz, P. M. Tulkens, T. R. Walsh, J. D. Watson, J. Witkowski, W. Witte, G. Wright, P. Yeh, and H. I. Zgurskaya. 2011. Tackling antibiotic resistance. Nature Review Microbiology 9:894-896.

Bush, K. and J. F. Fisher.  2011.  Epidemiological expansion, structural studies, and clinical challenges of new β-lactamases from Gram-negative bacteria.  Ann. Rev. Microbiol. 65:455-478.
Bush, K. and G. A. Jacoby. 2010. An updated functional classification of β-lactamases. Antimicrob. Agents Chemother. 54:969-976
Queenan, A. M., W. Shang, R. Flamm, and K. Bush. 2010. Hydrolysis and inhibition profiles of β-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. 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.

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.

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 β-lactamases.  Antimicrob. Agents Chemother. 39:1211-1233.

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