Dr. Susan Meschwitz receives the 2019 NIGMS RI-INBRE & COBRE Administrative Supplement Award
Dr. Susan Meschwitz, Associate Professor and Chairwoman of Chemistry at Salve Regina University, received the first NIGMS Administrative Supplement Award entitled “Quorum sensing antagonistic inhibition of medically important ESKAPE pathogens.” She is collaborating on her research with Dr. Helen (Beth) Fuchs, Assistant Professor of Medicine in the Warren Alpert Medical School of Brown University and Research Scientist at Rhode Island Hospital. Dr. Meschwitz said, “There is a significant need for new antibiotics with novel therapeutic targets. Our investigational compounds are quorum-sensing antagonists that we seek to determine the efficacy on a wide group of medically important pathogens. The quorum-sensing antagonists have a great deal of potential at inhibiting or disrupting bacterial biofilms, typically a challenge to treat.”
Dr. Meschwitz explained quorum sensing: “Many pathogenic bacteria rely on a communication system known as quorum sensing (QS) to regulate production of virulence factors, such as toxins, necessary for infection of a host. Blocking this communication system could potentially prevent bacterial pathogenesis with a lower risk of resistance development and thus could help to ease the threat of antibiotic resistance. Furthermore, it is believed that virulence disruption would also render the bacteria more sensitive to the effects of the immune system and conventional antibiotics. Thus, the disruption of QS should be pursued as a viable alternative to traditional antibiotics.”
“This collaboration has been a wonderful opportunity to further my research into the discovery of antimicrobial compounds that can inhibit medically important and drug resistant bacteria and has enabled the further training and education of undergraduate students.”
“Recently, we have identified three molecular scaffolds with promising inhibition (IC50 values 1.1-20.2 µM) of QS-controlled bacterial phenotypes. Our research aims to test 42 derived analogues to the 3 scaffolds for bacteria inhibition against the ESKAPE panel (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), a collection of clinically important bacteria that present drug resistance challenges. We will use these interrogations to identify the most effective chemical structures that contribute to bacterial inhibition and determine if these compounds provide synergy with the current antibiotic arsenal. Inhibitory compounds will be further scrutinized for efficacy using the invertebrate infection model Galleria mellonella (a larval form of the greater wax moth) to determine the therapeutic effects while also looking at the toxicity levels of the compounds. The information gained from the study is intended to provide insight about the most effective structural configuration for compounds that can antagonize quorum sensing for Gram-positive or Gram-negative bacteria so they can be followed up with future mammalian model studies.”
“This collaboration has been a wonderful opportunity to further my research into the discovery of antimicrobial compounds that can inhibit medically important and drug resistant bacteria and has enabled the further training and education of undergraduate students. My expertise is in the design and synthesis of potential quorum sensing inhibitors. In my lab, we are able to test these compounds in biosensor strains which gives us an idea of their potential as QS inhibitors. However, this collaboration with the Fuchs Lab at Rhode Island Hospital takes this research even further and allows for the testing of these compounds against a wide group of medically important pathogens. By marrying our efforts, we have been able to enhance our research efforts of developing new antimicrobial compounds.”