Associate Professor, Department of Biology
PhD, Wayne State University
Lay Research Summary
Bacterial infections are a very serious threat to public health today, mainly due to the ability of the bacteria to develop a resistance to almost all forms of antibiotics used in modern medicine. It has become clear that the bacteria possess a high potential for resistance against antibiotics due ...read moreto their ability to easily mutate their genetic information, coupled with the fact that the mutation of one bacterium affects the others as well (this is known as genetic “cross-talking”). The focus of the research team is to understand what biological mechanisms trigger resistance in infectious bacteria, especially the methicillin-resistant Staphylococcus aureus. This strain has managed to become resistant to nearly all antibiotics used in clinical practice, including a drug known as vancomycin, which is often used as a last resort. The bacterial and viral resistance phenomenon has raised some questions: is it possible to hinder bacterial or viral infections without causing resistance? In other words, is there such a thing as a resistance proof biological target? Biological targets are noted for the fact that their activity can be altered by an external stimulus. If there is a resistance-proof biological target, then what biological properties should it have? These are the questions that Dr. Golemi-Kotra and her team are looking to answer. There are two main strategies that are employed when attempting to inhibit the HIV infection: 1) developing vaccines, and 2) designing organic medications which hinder and prevent the different stages of the virus life-cycle from occurring. However, resistance development has led to slower progress in terms of results. In other words, viruses evolve to develop a resistance when exposed to drugs or a neutralizing antibody, which is a protein used by the immune system to identify and destroy foreign objects in the body, such as viruses or bacteria. The research team is particularly interested in looking at how the HIV virus fuses with the host cells of an organism, and the proteins which are involved with this step. Chemical and biological tools are implemented to study protein-protein interactions involved in this complex biophysical formation. The interactions will be analyzed from a quantitative perspective. read less
Scientific Research Summary
Bacterial infections have become a very serious issue of public health as a result of resistance developed or acquired toward almost all the antibiotics that are in use today. It has become clear that bacteria have the potential to develop resistance fairly easy toward an antibiotic ...read more due to the high mutagenesis rate of its genome and the genetic cross-talking among bacteria. Our focus is to understand the signaling mechanisms involved in induction of antibiotic resistance factors in pathogenic bacteria and especially in methicillin-resistant Staphylococcus aureus. This strain has acquired resistance to almost all the clinically used antibiotics including vancomycin, an antibiotic of the last resort. The phenomenon of bacterial and viral resistance has raised the questions: Can we inhibit bacterial or viral infections without giving rise to resistance. To put it differently: Is there a resistance-proof biological target? If this is possible, then what biological properties a resistance-proof target should have? Our group is investigating the answers to these questions and the solutions to these problems. Two main strategies have been pursued in inhibiting the HIV infection: (1) developing vaccines and (2) designing small molecules, organic- or peptide-based drugs that inhibit different stages of virus life-cycle. However, development of resistance has compromised the success in these efforts i.e. virus evolves to acquire a resistance when exposed to a neutralizing antibody or a drug. Our group is interested in looking closely at the fusion process of HIV virus with the host cells, and proteins involved in this step. The envelope glycoprotein complex is of special interest. Chemical and biological tools will be used to study the protein-protein interactions involved in the formation of this complex and biophysical methods will be used to quantitatively analyze these interactions.read less
Department of Chemistry, Faculty of Science
Expression, purification, crystallization and preliminary X-ray analysis of the receiver domain of Staphylococcus aureus LytR protein.
Journal: Acta Crystallogr Sect F Struct Biol Cryst Commun.
An electrospray ms-coupled microfluidic device for sub-second hydrogen/deuterium exchange pulse-labelling reveals allosteric effects in enzyme inhibition.
Journal: Lab Chip
Two unique phosphorylation-driven signaling pathways crosstalk in Staphylococcus aureus to modulate the cell-wall charge: Stk1/Stp1 meets GraSR.
Dual Roles of FmtA in Staphylococcus aureus Cell Wall Biosynthesis and Autolysis.
Journal: Agents Chemother.
Roles of DNA sequence and sigma A factor in transcription of the vraSR operon.
Journal: J Bacteriol.
Staphylococcus aureus methicillin-resistance factor fmtA is regulated by the global regulator SarA.
Journal: PLoS One
Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D Î²-lactamase from Acinetobacter baumannii.
Journal: J Biol Chem.
Phosphorylation-induced activation of the response regulator VraR from Staphylococcus aureus: insights from hydrogen exchange mass spectrometry.
Journal: J Mol Biol.
DNA-binding activity of the vancomycin resistance associated regulator protein VraR and the role of phosphorylation in transcriptional regulation of the vraSR operon.
Phosphorylation-dependent conformational changes and domain rearrangements in Staphylococcus aureus VraR activation.
Journal: Proc Natl Acad Sci U S A.
Sylvie MorinDepartment of ChemistryFaculty of Science
Michael SiuDepartment of ChemistryFaculty of Science
Derek WilsonDepartment of ChemistryFaculty of Science
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