I focus on the molecular mechanisms of antibiotic resistance and structure-function studies of Class A beta-lactamases.
Research Information
Research Interests
Among the major problems faced in medicine, resistance to antibiotics is regarded as a singular challenge. The primary focus of our laboratory is to understand the genetic and amino acid sequence determinants of the enzymes that inactivate ß-lactams, the ß-lactamases. Our current work is directed at solving three main problems:
- how ß-lactamase inhibitors inactivate -lactamases;
- how ß-lactamases hydrolyze advanced generation cephalosporins; and
- how mutations impact upon ß-lactamase expression. We are also interested in how penicillin interacts with penicillin resistant PBPs and the molecular epidemiology of extended spectrum ß-lactamases (ESBLs).
Lab Members: Andrea M. Hujer, Christopher R. Bethel
Collaborators: Dr. Marion S. Helfand, Dr. Curtis J. Donskey, Dr. Louis B. Rice, Dr. David L. Paterson, Dr. Focco van den Akker, Dr. Paul R. Carey, Dr. Vernon E. Anderson, Dr. James R. Knox, Dr. Malcolm Page, Dr. Lily Ng, Dr. John Buynak, Dr. Shu Chen, Dr. Michael Kinter, Dr. Anthony Fink, Dr. John Quinn.
External Appointments
Publications
- Guerrero DM, Perez F, Conger NG, Solomkin JS, Adams MD, Rather PN, Bonomo RA. Acinetobacter baumannii-associated skin and soft tissue infections: recognizing a broadening spectrum of disease. Surg Infect (Larchmt). 2010 Feb;11(1):49-57. Review. PubMed PMID: 19788383; PubMed Central PMCID: PMC2956563.
- Drawz SM, Babic M, Bethel CR, Taracila M, Distler AM, Ori C, Caselli E, Prati F, Bonomo RA. Inhibition of the class C beta-lactamase from Acinetobacter spp.:insights into effective inhibitor design. Biochemistry. 2010 Jan 19;49(2):329-40. PubMed PMID: 19925018; PubMed Central PMCID: PMC2810401.
- Endimiani A, Patel G, Hujer KM, Swaminathan M, Perez F, Rice LB, Jacobs MR, Bonomo RA. In vitro activity of fosfomycin against blaKPC-containing Klebsiella pneumoniae isolates, including those nonsusceptible to tigecycline and/or colistin. Antimicrob Agents Chemother. 2010 Jan;54(1):526-9. PubMed PMID: 19901089; PubMed Central PMCID: PMC2798518.
- Drawz SM, Bonomo RA. Three decades of beta-lactamase inhibitors. Clin Microbiol Rev. 2010 Jan;23(1):160-201. Review. PubMed PMID: 20065329; PubMed Central PMCID: PMC2806661.
- Bou G, Santillana E, Sheri A, Beceiro A, Sampson JM, Kalp M, Bethel CR, Distler AM, Drawz SM, Pagadala SR, van den Akker F, Bonomo RA, Romero A, Buynak JD. Design, synthesis, and crystal structures of 6-alkylidene-2'-substituted penicillanic acid sulfones as potent inhibitors of Acinetobacter baumannii OXA-24 carbapenemase. J Am Chem Soc. 2010 Sep 29;132(38):13320-31. PubMed PMID:20822105.
- Endimiani A, Perez F, Bajaksouzian S, Windau AR, Good CE, Choudhary Y, Hujer AM, Bethel CR, Bonomo RA, Jacobs MR. Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced carbapenem susceptibility. J Clin Microbiol. 2010 Dec;48(12):4417-25. PubMed PMID: 20881179; PubMed Central PMCID: PMC3008460.