Karen Bush

Karen Bush is an American biochemist. She is a biology professor at Indiana University and the interim director of the university's biotechnology program. Bush conducts research focusing on bacterial resistance mechanisms to beta-lactam antibiotics.[1]

Education

Bush received her BA, magna cum laude from Monmouth College in 1965, with a major in chemistry and a minor in math-physics. In 1970 Bush graduated from Indiana University Bloomington with her Ph.D. in biochemistry under Henry R. Mahler.[2][3] Bush was a postdoctoral fellow at University of California, Santa Barbara from 1970 to 1971.[1]

Scientific contributions

Bush is internationally known for her research on the discovery and characterization of beta-lactamases, the family of enzymes that confer resistance to penicillins and cephalosporins.  Antibiotic resistance has emerged as a key threat to the global fight against infectious diseases, and Bush’s research into the mechanisms of action for beta-lactamases has provided key insights in development of beta-lactamase inhibitors to combat these modes of resistance. Her review article on beta-lactamases established commonly used nomenclature.[4]  She co-curated a website for this family of enzymes that has named over 2000 beta lactamases.[5]

During her 36 years of antibiotic discovery efforts in the pharmaceutical industry, Bush worked on the research teams that brought 9 anti-infective leads to clinical trials and 5 antibiotics to FDA and/or EMA approval (aztreonam, piperacillin-tazobactam, levofloxacin, doripenem and ceftobiprole).  As a Professor, Bush has continued to lead research characterizing beta-lactam resistance in enteric bacteria and collaborates with pharmaceutical companies in evaluating clinical potential of novel antibacterial agents by studying the spectrum of activity and mechanisms of resistance.  This work has been included in data packages submitted to the FDA for drug approval, and  research from her laboratory has supported the approval process for 6 new antibacterial therapies (ceftolozane-tazobactam, ceftazidime-avibactam, plazomicin, eravacycline, imipenem-relebactam and cefiderocol).

Professional career

After completing her postdoctoral research, Bush became an instructor of biochemistry in the University of North Carolina Chapel Hill School of Medicine for a year before serving as an Assistant Professor of Chemistry at the University of Delaware from 1972 to 1973. She then started an 18 year stint at The Squibb Institute for Medical Research in Princeton, NJ, spending her first 5 years in the analytical chemistry department beginning her research on beta-lactamases and beta-lactamase inhibitors. While at The Squibb Institute, Bush was part of the team that discovered Aztreonam and rose from a Research Investigator position to increasing leadership and research scientist roles, ultimately named not only a Principal Investigator but also as a Research Leader and a Research Fellow. She then went on to American Cynamid/American Home Products/Wyeth-Aherst in Pearl River NJ. Continuing her research and discovery efforts in antibiotic chemotherapy where she led teams that discovered a new carbapenem and supported the registration and launch of piperacillin-tazobactam (Zosyn®). After a year as Director of Microbial Biochemistry at the Astra Research Center in Boston, Bush moved on to lead antibacterial discovery teams at Johnson & Johnson Pharmaceutical Research & Development, Raritan NJ from 1997 to 2009 when she became an independent consultant to a number of pharmaceutical and biotechnology companies. In 2013, Bush returned academia to leading research projects, to teach and mentor graduate students , and is now a Professor of Practice in Biotechnology and the Interim Director of Biotechnology at Indiana University in Bloomington, IN.

Awards and honors

In recognition of her outstanding research in antibiotic chemotherapy, Bush received the Hamao Umezawa Memorial Award on November 24, 2017 at the 30th annual meeting for the International Society of Chemotherapy for Infection and Cancer, held in Taipei, Taiwan.[6] She was the first woman to receive this award.[3]

Within the American Society of Microbiology, she was elected as a Fellow of the American Academy of Microbiology in 2000[7] and selected as the ICAAC Lecturer in 2004.

In 2015 she was awarded the "Excellence in Standards Award" from the Clinical and Laboratory Standards Institute (CLSI).[7]

Professional activities

As a world recognized expert in the field of antibiotic discovery, Bush is involved in numerous scientific communities and services.

Publications

Bush has authored over 225 peer-reviewed publications with over 30,000 citations and an h-index of 79.[12] She has co-authored 25 book chapters, edited a book, made over 225 scientific presented at international meetings, and been an invited speaker at over 100 scientific meetings or symposia. She is an inventor on 10 issued US patents.[13]

Representative publications include:

  • Theuretzbacher U, Bush K, Harbarth S, Paul M, Rex JH, Tacconelli E, Thwaites GE. 2020. Critical analysis of antibacterial agents in clinical development. Nature Rev. Microbiol. 18:286-298
  • Mack AR, Barnes MD, Taracila MA, Hujer AM, Hujer KM, Cabot G, Feldgarden M, Haft DH, Klimke W, van den Akker F, Vila AJ, Smania A, Haider S, Papp-Wallace KM, Bradford PA, Rossolini GM, Docquier JD, Frere JM, Galleni M, Hanson ND, Oliver A, Plesiat P, Poirel L, Nordmann P, Palzkill TG, Jacoby GA, Bush K, Bonomo RA. 2019. A standard numbering scheme for class C beta-lactamases. Antimicrob. Agents Chemother. 11:11.[14]
  • 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.[15]
  • 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.[16]
  • Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54(3):969-976.[17]
  • Queenan, A. M., W. Shang, K. Bush, and R. K. Flamm.  2010.  Differential selection of single-step AmpC or efflux mutants of Pseudomonas aeruginosa by using cefepime, ceftazidime, or ceftobiprole.  Antimicrob. Agents Chemother. 54: 4092–4097.[18]
  • Morrow B. J., W. He, K. M. Amsler, B. D. Foleno, M. J. Macielag, A. S. Lynch, and K. Bush.  2010. In vitro antibacterial activities of JNJ-Q2, a new broad-spectrum fluoroquinolone.  Antimicrob. Agents Chemother.  54:1955-1964.[19]
  • Kao, L. .M., K.  Bush, R.. Barnewall, J. Estep, F. W. Thalacker , P. H. Olson, G. L. Drusano, N. Minton, S. Chien, A. Hemeryck, and M. F. Kelley MF. 2006. Pharmacokinetic considerations and efficacy of levofloxacin in an inhalational anthrax (postexposure) rhesus monkey model. Antimicrob. Agents Chemother. 50 3535-3542.[20]
  • Queenan, A. M., Torres-Viera, C., Gold, H. S., Carmeli, Y., Eliopoulos, G. M., Moellering, R. C., Jr, Quinn, J. P., Hindler, J., Medeiros, A. A., & Bush, K. (2000). SME-type carbapenem-hydrolyzing class A beta-lactamases from geographically diverse Serratia marcescens strains. Antimicrobial agents and chemotherapy, 44(11), 3035–3039.[21]
  • Bush, K.,G. A. Jacoby and A. A. Medeiros.  1995.  A functional classification scheme for beta-lactamases.  Antimicrob. Agents Chemother. 39:1211-1233.[22]
  • Rasmussen, B. A., P. A. Bradford, J. P. Quinn, J. Wiener, R. A. Weinstein, and K. Bush.  1993.  Genetically diverse ceftazidime-resistant isolates from a single center: Biochemical and genetic characterization of TEM-10 beta-lactamases encoded by different nucleotide sequences.  Antimicrob. Agents Chemother. 37:1989-1992.[23]
  • Bush K, Macalintal C, Rasmussen BA, Lee VJ, Yang Y. Kinetic interactions of tazobactam with beta-lactamases from all major structural classes. Antimicrob Agents Chemother. 1993;37(4):851-858.[24]
  • Bush, K., S. K. Tanaka, D. Bonner and R. B. Sykes.  1985.  Resistance caused by decreased penetration of beta-lactam antibiotics into Enterobacter cloacae.  Antimicrob. Agents Chemother. 27:555-560.[25]
  • Sykes, R. B., C. M. Cimarusti, D. P. Bonner, K. Bush, D. M. Floyd, N. H. Georgopapadakou, W. H. Koster, W. C. Liu, W. L. Parker, P. A. Principe, M. L. Rathnum, W. A. Slusarchyk, W. H. Trejo and J. S. Wells, Jr.  1981.  Monocyclic beta-lactam antibiotics produced by bacteria.  Nature 291:489-491.[26]
  • Bush K, Bonner DP, Sykes RB. Izumenolide-a novel beta-lactamase inhibitor produced by Micromonospora. II. Biological properties. J Antibiot (Tokyo). 1980;33(11):1262-1269.[27]

References
  1. "Karen Bush".
  2. "Karen Bush Watts '65 to speak to science students". www.monmouthcollege.edu. Retrieved 2019-12-24.
  3. "Bush receives international award for contributions to antimicrobial chemotherapy". Department of Biology. Retrieved 2020-07-20.
  4. Bush, Karen (2013). "The ABCD's of β-lactamase nomenclature". Journal of Infection and Chemotherapy. 19 (4): 549–559. doi:10.1007/s10156-013-0640-7. ISSN 1341-321X. PMID 23828655. S2CID 13657047.
  5. "Studies Page". externalwebapps.lahey.org. Retrieved 2020-11-17.
  6. "Karen Bush is first woman to receive Hamao Umezawa Memorial Award". 28 September 2017.
  7. manager, Community. "Karen Bush". REVIVE. Retrieved 2020-07-21.
  8. "Karen Bush, Ph.D." ASM.org. Retrieved 2020-11-17.
  9. Bush, Karen (2010). "Bench-to-bedside review: The role of β-lactamases in antibiotic-resistant Gram-negative infections". Critical Care. 14 (3): 224. doi:10.1186/cc8892. ISSN 1364-8535. PMC 2911681. PMID 20594363.
  10. "Advisory Board". Carb-X. Retrieved 2020-11-17.
  11. manager, Community. "Karen Bush". REVIVE. Retrieved 2020-11-17.
  12. "Karen Bush - Google Scholar". scholar.google.com. Retrieved 2020-07-21.
  13. "Patent Database Search Results: IN/Bush AND IN/Karen in US Patent Collection". patft.uspto.gov. Retrieved 2020-07-21.
  14. Mack, Andrew R.; Barnes, Melissa D.; Taracila, Magdalena A.; Hujer, Andrea M.; Hujer, Kristine M.; Cabot, Gabriel; Feldgarden, Michael; Haft, Daniel H.; Klimke, William; Akker, Focco van den; Vila, Alejandro J. (2020-02-21). "A Standard Numbering Scheme for Class C β-Lactamases". Antimicrobial Agents and Chemotherapy. 64 (3). doi:10.1128/AAC.01841-19. ISSN 0066-4804. PMC 7038296. PMID 31712217.
  15. Zhang, Yunliang; Kashikar, Ankita; Brown, C. Adam; Denys, Gerald; Bush, Karen (2017). "Unusual Escherichia coli PBP 3 Insertion Sequence Identified from a Collection of Carbapenem-Resistant Enterobacteriaceae Tested In Vitro with a Combination of Ceftazidime-, Ceftaroline-, or Aztreonam-Avibactam". Antimicrobial Agents and Chemotherapy. 61 (8): e00389–17, e00389–17. doi:10.1128/AAC.00389-17. ISSN 0066-4804. PMC 5527577. PMID 28559260.
  16. Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A.; Kishony, Roy; Kreiswirth, Barry N.; Kutter, Elizabeth; Lerner, Stephen A. (2011). "Tackling antibiotic resistance". Nature Reviews Microbiology. 9 (12): 894–896. doi:10.1038/nrmicro2693. ISSN 1740-1526. PMC 4206945. PMID 22048738.
  17. Bush, Karen; Jacoby, George A. (2010). "Updated Functional Classification of β-Lactamases". Antimicrobial Agents and Chemotherapy. 54 (3): 969–976. doi:10.1128/AAC.01009-09. ISSN 0066-4804. PMC 2825993. PMID 19995920.
  18. Queenan, Anne Marie; Shang, Wenchi; Bush, Karen; Flamm, Robert K. (2010). "Differential Selection of Single-Step AmpC or Efflux Mutants of Pseudomonas aeruginosa by Using Cefepime, Ceftazidime, or Ceftobiprole". Antimicrobial Agents and Chemotherapy. 54 (10): 4092–4097. doi:10.1128/AAC.00060-10. ISSN 0066-4804. PMC 2944577. PMID 20606064.
  19. Morrow, B. J.; He, W.; Amsler, K. M.; Foleno, B. D.; Macielag, M. J.; Lynch, A. S.; Bush, K. (2010-05-01). "In Vitro Antibacterial Activities of JNJ-Q2, a New Broad-Spectrum Fluoroquinolone". Antimicrobial Agents and Chemotherapy. 54 (5): 1955–1964. doi:10.1128/AAC.01374-09. ISSN 0066-4804. PMC 2863672. PMID 20176911.
  20. Li, Fang; Nandy, Partha; Chien, Shuchean; Noel, Gary J.; Tornoe, Christoffer W. (2010). "Pharmacometrics-Based Dose Selection of Levofloxacin as a Treatment for Postexposure Inhalational Anthrax in Children". Antimicrobial Agents and Chemotherapy. 54 (1): 375–379. doi:10.1128/AAC.00667-09. ISSN 0066-4804. PMC 2798547. PMID 19858256.
  21. Queenan, Anne Marie; Torres-Viera, Carlos; Gold, Howard S.; Carmeli, Yehuda; Eliopoulos, George M.; Moellering, Robert C.; Quinn, John P.; Hindler, Janet; Medeiros, Antone A.; Bush, Karen (2000-11-01). "SME-Type Carbapenem-Hydrolyzing Class A β-Lactamases from Geographically Diverse Serratia marcescens Strains". Antimicrobial Agents and Chemotherapy. 44 (11): 3035–3039. doi:10.1128/AAC.44.11.3035-3039.2000. ISSN 0066-4804. PMC 101599. PMID 11036019.
  22. Bush, K.; Jacoby, G. A.; Medeiros, A. A. (1995-06-01). "A functional classification scheme for beta-lactamases and its correlation with molecular structure". Antimicrobial Agents and Chemotherapy. 39 (6): 1211–1233. doi:10.1128/AAC.39.6.1211. ISSN 0066-4804. PMC 162717. PMID 7574506.
  23. Rasmussen, B A; Bradford, P A; Quinn, J P; Wiener, J; Weinstein, R A; Bush, K (1993-09-01). "Genetically diverse ceftazidime-resistant isolates from a single center: biochemical and genetic characterization of TEM-10 beta-lactamases encoded by different nucleotide sequences". Antimicrobial Agents and Chemotherapy. 37 (9): 1989–1992. doi:10.1128/AAC.37.9.1989. ISSN 0066-4804. PMC 188106. PMID 8239618.
  24. Bush, K; Macalintal, C; Rasmussen, B A; Lee, V J; Yang, Y (1993-04-01). "Kinetic interactions of tazobactam with beta-lactamases from all major structural classes". Antimicrobial Agents and Chemotherapy. 37 (4): 851–858. doi:10.1128/AAC.37.4.851. ISSN 0066-4804. PMC 187782. PMID 8388201.
  25. Bush, K; Tanaka, S K; Bonner, D P; Sykes, R B (1985-04-01). "Resistance caused by decreased penetration of beta-lactam antibiotics into Enterobacter cloacae". Antimicrobial Agents and Chemotherapy. 27 (4): 555–560. doi:10.1128/AAC.27.4.555. ISSN 0066-4804. PMC 180094. PMID 3873900.
  26. YOSHIDA, CHOSAKU; HORI, TAKAKO; MOMONOI, KAISHU; NAGUMO, KATSUYUKI; NAKANO, JOJI; KITANI, TETSUMI; FUKUOKA, YOSHIKAZU; SAIKAWA, ISAMU (1985). "Studies on monocyclic .BETA.-lactam antibiotics. II. Synthesis and antibacterial activity of 3-acylamino-2-azetidinone-1-oxysulfonic acids". The Journal of Antibiotics. 38 (11): 1536–1549. doi:10.7164/antibiotics.38.1536. ISSN 0021-8820. PMID 4077733.
  27. Bush, Karen; Bonner, Daniel P.; Sykes, Richard B. (1980). "Izumenolide - a novel .BETA.-lactamase inhibitor produced by Micromonospora. II. Biological properties". The Journal of Antibiotics. 33 (11): 1262–1269. doi:10.7164/antibiotics.33.1262. ISSN 0021-8820. PMID 6972939.
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