Sergei Vakulenko
University of Notre Dame, IN·Microbiology & Immunology
Acinetobacter baumannii is a bacterium that causes deadly infections. The US Centers for Disease Control and Prevention lists it as a serious antibiotic resistance threat.
- Fields
Microbiology & Immunology
Biochemistry
Pharmacology
- Topics
Acinetobacter baumannii
antibiotic resistance
antimicrobial resistance
- Grants
- 1 known grant, through Mar 2027
What they work on
- Measure the activity of novel carbapenems against A. baumannii strains producing major CHDLs (enzymes that destroy carbapenems) and other carbapenemases, and use enzyme kinetics and structural studies to explain how the compounds inhibit these enzymes.
- Study how the new carbapenems bind penicillin-binding proteins (PBPs), the bacterial enzymes they target, and determine how much efflux pumps and porin channels contribute to bacterial resistance to them.
- Design and characterize several dozen new carbapenems with stronger carbapenemase inhibition, better PBP binding, faster entry into bacterial cells and greater resistance to being pumped out.
- Test the solubility, stability and toxicity of the best new carbapenems in vitro, then evaluate them in animal studies as potential treatments for multidrug-resistant A. baumannii.
More about the research
Carbapenems, last-resort antibiotics, were once the drugs of choice against it. Now resistance to carbapenems reaches up to 90% in some parts of the world, and many strains also resist other classes of antibiotics. Up to half of patients with these infections die. The long-term goal of this work is to develop new antibiotics for multidrug-resistant A. baumannii.
Why it matters
Carbapenem-resistant A. baumannii infections kill up to half of affected patients, and few treatment options remain. New carbapenems that resist and block the bacterium's antibiotic-destroying enzymes could become new treatments for patients with these deadly multidrug-resistant infections.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
George Drusano
University of Florida, FL·Pharmacology
Determine dose-response and resistance-suppression targets for newer antibiotics that lack such data, using dose-ranging and dose-fractionation experiments in the hollow fiber infection model, which reproduces human drug concentration profiles over days.
Michael Stephen Trent
University of Georgia, GA·Microbiology & Immunology
Develop an analytical tool that measures LPS molecules in transit, and combine it with mass spectrometry of the enzyme LpxC and LPS precursors to determine how the YejM-YciM system controls LPS production in E. coli.
Herve Roy
University of Central Florida, FL·Microbiology & Immunology
Screen a library of boron-containing compounds with a continuous multiplexed assay that monitors up to four Mycobacterium tuberculosis aminoacyl-tRNA synthetases at once, probing class II enzymes that have not been explored as drug targets.
The school
University of Notre Dame: 19 labs on PI Pages, $346M a year on research, 277 research doctorates a year.
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