Prof. J.P. Gerdt
Title: Chemical Inhibition of Bacterial Immune Systems
Bio: Dr. Gerdt obtained his B.S. in Chemistry in 2008 from the University of Illinois in Urbana-Champaign, where he researched the chemistry and folding of nucleic acids with Scott Silverman. He then moved to the University of Wisconsin–Madison, where he studied the chemistry of cell-cell signaling in bacteria with Helen Blackwell. After earning his Ph.D. in Chemistry in 2014, he joined the laboratory of Jon Clardy at Harvard Medical School. As an NIH-funded postdoctoral fellow in the Clardy lab, he researched interkingdom chemical signaling in choanoflagellates and in Plasmodium falciparum—a parasite that causes malaria. Dr. Gerdt started his independent career in the Department of Chemistry at Indiana University in 2019. By integrating analytical, organic, and biological chemistry with microbiology and cell biology, the Gerdt lab uncovers the molecules that shape microbial symbioses. The Gerdt lab has discovered several natural products and synthetic compounds that impact the ability of bacteriophages to kill pathogenic bacteria. The lab has also discovered multicellularity signaling mechanisms that may have shaped the origins of the first animals. Moreover, the Gerdt lab has discovered new metabolite mediators of inter-bacterial competition. Dr. Gerdt is a recipient of the NIH Maximizing Investigators’ Research Award (2020), NSF CAREER Award (2021), Trustees Teaching Award (2023), and Camille-Dreyfus Teacher-Scholar Award (2024).
Abstract: Bacteria get “sick” too. A substantial fraction of our world’s bacteria are killed each day by viruses called bacteriophages (phages). These natural predators are promising alternatives to antibiotics in the clinic, in agriculture, and in other industries. However, bacteria have evolved myriad immune systems that afford resistance to phages. These immune systems may render phage therapies ineffective. Until now, these immune systems have not been probed with chemical inhibitors. My laboratory has begun to fill this void with newly discovered small molecule inhibitors of several anti-phage immune systems. Of note, we have discovered chemical inhibitors of Thoeris and CBASS defense systems as well as cell surface alanylation defenses. We have employed these inhibitors as probes to uncover the mechanisms and significance of each defense system. Furthermore, we are leveraging the inhibitors to re-sensitize phage-resistant pathogens to phage-based antibacterial therapies. Beyond synthetic small molecule inhibitors, we have also discovered multiple natural products that may already be influencing the sensitivity of bacteria to phages in diverse microbiomes.
Keywords: Chemical probes, bacteriophages, natural products, high-throughput screening