- Postdoctoral Fellow, University of California, Santa Barbara, 1970-1971
- Ph.D., Indiana University Bloomington, 1970
Professor of Practice, Biotechnology
Professor of Practice, Biotechnology
Note to prospective graduate students: The Bush lab is not accepting any new students.
Following postdoctoral work, I joined the Squibb Institute for Medical Research in New Jersey and began studying beta-lactamases, enzymes in pathogenic bacteria that cause 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®). We also worked with medicinal chemists to discover novel monobactams, carbapenems, oxazolidinones, and topoisomerase inhibitors, resulting in six drugs that entered human clinical trials. My laboratory published studies examining the mechanism of action of penicillin-binding proteins (PBPs) and beta-lactamases, focusing on the role of natural variants of these enzymes. I have authored review articles that established a commonly used beta-lactamase nomenclature, and was co-curator of a website responsible for naming more than 2000 beta-lactamases.
My current laboratory has focused on characterizing resistance mechanisms to beta-lactam antibiotics in enteric bacteria. Studies from my lab have alerted healthcare facilities in the greater Indianapolis area to the need for increased infection control to minimize the risk from carbapenem-resistant Enterobacteriaceae ("CRE"), pathogens deemed by the CDC to pose an Urgent Threat to the clinical community. My lab has also collaborated 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. During these studies, we have also identified unusual resistance characteristics. Five of the agents, ceftolozane-tazobactam, ceftazidime-avibactam, plazomicin, eravacycline and imipenem-relebactam, gained FDA approval following our testing.
Bush K, Bradford PA. 2019. Interplay between β-lactamases and new β-lactamase inhibitors. Nature Reviews Microbiology 17:295-306. doi.org/10.1038/s41579-019-0159-8
Bush K. 2018. Past and present perspectives on β-lactamases. Antimicrobial Agents & Chemotherapy 62:e01076-18. dx.doi.org/10.1128/AAC.01076-18
Bush K. A Meandering Path from Biochemist to Microbiologist. ACS Infectious Diseases. 2018-12-04. DOI: 10.1021/acsinfecdis.8b00261.
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.
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.
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