Sergei Vakulenko, Research Associate Professor of Chemistry and Biochemistry, has received two five-year grants from the National Institutes of Health totaling $3.75 million. Both grants were awarded to conduct research aimed at the elucidation of mechanisms of antibiotic resistance in clinical bacterial pathogens. Antibiotic-resistant bacteria can cause serious, often life-threatening infections, and therapeutic options for such infections are very limited.
Dr. Vakulenko’s laboratory will study mechanisms of resistance to two major classes of antibiotics, beta-lactams and aminoglycosides. Resistance to these drugs arises due to the bacterial production the of antibiotic-inactivating enzymes known as class A carbapenemases and aminoglycoside phosphotransferases. Multidisciplinary approaches that include molecular biology, protein chemistry, detailed enzymology, and structural analyses of the native enzymes and their complexes with products, substrate and substrate analogs will be used to elucidate the mechanistic aspects of these clinically important enzymes providing detailed knowledge of how they perform their catalytic functions. Another important aim of the proposed studies is to evaluate the evolutionary potential of these enzymes towards broadening the spectrum of conferred antibiotic resistance. Ultimately, such knowledge will provide important guidance for the future utility of beta-lactam and aminoglycoside antibiotics and establish the basis for the design of new inhibitors of class A carbapenemases and aminoglycoside phosphotransferases for the treatment of life-threatening infections.