Robert Bonomo, M.D.
Professor of Medicine, Pharmacology, and Molecular Biology and Microbiology
Geriatric Care Center 111C (W)
12200 Fairhill Rd.
Cleveland, OH 44120
Research Service
Veterans Affairs Medical Center
10701 East Blvd.
Cleveland. OH 44106
Phone: (216) 791-3800 x4399
Fax: (216) 229-8509
E-mail: rab14@case.edu
Research
Bacterial resistance to beta-lactams is threatening the most potent antibiotics
we have. The research interests in our laboratory involve understanding the structure
function relationships of the class A beta-lactamase, SHV-1. This chromosomal and
plasmid encoded beta-lactamase is usually found in Klebsiella pneumonia and confers
high level resistance to third generation cephalosporins (cefotaxime, ceftazidime,
and aztreonam). This resistance can render ineffective the most frequently used
drugs to treat serious nosocomial infections. Our goals are to understand what amino
acid substitutions permit evolution of novel substrate profiles and what factors
control expression of these periplasmic enzymes. By using site directed mutagenesis
and immunological tools to quantify expression, we are able to draw conclusions
as to why these highly resistant variants may have arisen in nature. We are also
interested in quantifying beta-lactamase expression in organisms harboring Class
C beta-lactamases. We have developed antibodies able to detect the presence of this
class of enzymes in clinical strains, thereby facilitating molecular epidemiological
investigations.
SELECTED REFERENCES:
Lin, S., Thomas, M., Bonomo, R.A.. 1999. OHIO-1 b-lactamase mutants: The
Arg 244Ser mutation and resistance to b-lactams and b-lactamase inhibitors, Biochem
Biophys Acta, 1432 15: 125-136.
Kuzin, A., Nukaga, M., Nukaga, Y., Hujer, A.M., Bonomo, R.A., Knox, J.R.
1999. Structure of SHV-1 b-lactamase, Biochemistry, 38: 5720-5727.
Tzouvelekis, L.S., Bonomo, R.A. 1999. SHV-type b-lactamases. Current Pharmaceutical
Design 5, 847-864.
Rice L.B., Carias, L.L., Hujer, A.M., Bonafede, M., Hutton, R., Bonomo, R.A.
2000 High-level expression of chromosomally encoded SHV-1 and an outer membrane
protein change conferring Klebsiella pneumoniae. Antimicrob Agents Chemother
44:362-367.