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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 American Society for Microbiology (2014)

Monmouth College Hall of Achievement Award (2015)

CLSI Excellence in Standards Development Award (2015)

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 helped develop the antibiotics aztreonam (Azactam), piperacillin-tazobactam (Zosyn), levofloxacin (Levaquin), doripenem (Doribax) and the anti-MRSA cephalosporin ceftobiprole (Zeftera). During that time my laboratory published studies examining the mechanism of action of penicillin-binding proteins (PBPs) and characterization of various beta-lactamases that interact with the beta-lactam antibiotics. I also established one of the most commonly used beta-lactamase nomenclature schemes. As the head of the Antimicrobial Drug Discovery Research at J&J, my team developed a number of high-throughput screening assays that identified novel inhibitors of bacterial enzyme targets. We also 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 known for characterizing new beta-lactamases and their interactions with various beta-lactam antibiotics.  Our lab currently collaborates with several groups to characterize beta-lactam-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
Zhang Y., X. Lin and K. Bush. 2016. In vitro susceptibility of b-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline. J. Antibiotics 69:600-604
Kao, C., X. Lin, G. Yi, Y. Zhang, D. A. Rowe-Magnus, and K Bush. 2016. Cathelicidin antimicrobial peptides with reduced activation of Toll-like receptor signaling have potent bactericidal activity against colistin-resistant bacteria. mBio 7(5):e01418-16. doi:10.1128/mBio.01418-16.
Bush K. 2015. Antibiotics: Synergistic MRSA combinations. Nature Chem. Biol. 11:832-833
Li, H. M. Estabrook, G. J. Jacoby, W. W. Nichols, R. T. Testa, and K. Bush. 2015. In vitro susceptibility of characterized β-lactamase-producing strains tested with avibactam combinations. Antimicrob. Agents Chemother. 59:1789 –1793
Bush, K. 2015. What kind of new agents do we need to treat Gram-negative bacterial infections? ACS Infect. Dis. 1: 509-511.
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.
Page, M. G. P. and K. Bush. 2014. Discovery and development of new antibacterial agents targeting Gram-negative bacteria in the era of pandrug resistance: is the future promising? Curr. Opin. Pharmacol. 18:91–97
Bush, K.  2013.  Carbapenemases: Partners in crime.    J. Global Antimicrob. Resis. 1:7–16
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.  2013.  The ABCD’s of b-lactamase nomenclature.  J. Infect. Chemother. 19:549-559

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. 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., 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.

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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