- Postdoctoral Fellow, University of California, Santa Barbara, 1970-1971
- Ph.D., Indiana University Bloomington, 1970
Professor of Practice, Biotechnology
Professor of Practice, Biotechnology
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. While in the pharmaceutical industry (Squibb; Lederle/Wyeth; Johnson & Johnson), 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 published studies examining the mechanism of action of penicillin-binding proteins (PBPs), the role of mutant PBPs in antibiotic resistance, and the interactions of various beta-lactamases 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. At Lederle and as the head of the Antimicrobial Drug Discovery Research team at J&J, I led the development of a number of high-throughput screening assays that identified novel inhibitors of bacterial enzymes. My teams also worked closely with medicinal chemists to discover novel monobactams, carbapenems, oxazolidinones, and topoisomerase inhibitors, resulting in six drugs that entered human clinical trials.
My current laboratory has focused on characterizing resistance mechanisms to beta-lactam antibiotics in enteric bacteria. Studies from my lab have alerted health care facilities in the greater Indianapolis area to the need for increased infection control to minimize the risk from carbapenem-resistant Enterobacteriaceae ("CRE"); these pathogens have been deemed by the CDC to pose an Urgent Threat to the health care community. My lab is also collaborating with several pharmaceutical companies to characterize the antibacterial activity of new investigational drugs against these resistant bacteria, providing information that is shared with the FDA in the drug approval process. Two of the agents tested, Zerbaxa® and Avycaz® have recently gained FDA approval. During these studies, we have identified unusual resistance characteristics to some of these new agents.
Zhang, Y., A. Kashikar, C. A. Brown, G. Denys, and K. Bush. 2017. An unusual E. coli PBP3 insertion sequence identified from a collection of carbapenem-resistant Enterobacteriaceae (CRE) tested in vitro with ceftazidime-, ceftaroline- or aztreonam-avibactam combinations. Antimicrob. Agents Chemother. August 2017 61:e00389-17; Accepted manuscript posted online 30 May 2017 , doi:10.1128/AAC.00389-17.
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.
Zhang Y., X. Lin and K. Bush. 2016. In vitro susceptibility of β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline. J. Antibiotics 69:600-604.
Li, H. M. Estabrook, G. A. 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.
Estabrook, M., M. B. Bussell, S. L. Clugston and K. Bush. 2014. In vitro activity of ceftolozane-tazobactam as determined by broth dilution and agar diffusion assays against recent U.S. Escherichia coli isolates from 2010 to 2011 carrying CTX-M-Type Extended-Spectrum β-Lactamases. J. Clin. Microbiol. 52:4049-4052.
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. Antimicrob. Agents Chemother. 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.
Yigit, H., A. M. Queenan, G. J. Anderson, A. Domenech-Sanchez, J. W. Biddle, C. D. Steward, S. Alberti, K. Bush and F. C. Tenover. 2001. Characterization of a novel carbapenem hydrolyzing β-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 45:1151-1161.
Bush, K.,G. A. Jacoby and A. A. Medeiros. 1995. A functional classification scheme for β-lactamases. Antimicrob. Agents Chemother. 39:1211-1233