Project Summary The International Conference on Gram-Positive Pathogens (ICGPP) brings together scientists at all stages of their careers to exchange ideas and research strategies stemming from shared interests in gram-positive pathogens. This conference, initially held in 2006 and then continued in 2008, 2010, 2012, 2014, 2016, and 2018 because of participant enthusiasm, grew out of collaborations between investigators at the University of Nebraska Medical Center and other academic institutions in the great plains region of the United States. The overarching benefit of ICGPP is the opportunity for investigators to share the science, approaches, and protocols that are unique to gram-positive bacteria in contrast to gram-negative bacteria. While gram-positive pathogens cause myriad infections, ranging from antibiotic-associated colitis to necrotizing fasciitis, fundamental aspects of biological function such as protein secretion across single membranes, cell wall biosynthesis and protein anchoring, and cell-cell communication are shared between this group of medically important bacteria. The impact of gram-positive infections continues to grow, and antibiotic resistance remains a significant threat. As an example, Clostridioides difficile enterocolitis, once primarily associated with antibiotic use in hospitals, is now found in young, healthy adults that do not have an epidemiological relationship to a healthcare facility. Recent data suggests that infections caused by C. difficile are the leading cause of mortality among antibiotic-resistant bacteria in the US. In addition, community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300 continues to cause skin and soft tissue infections in schools, locker rooms, and hospitals in otherwise healthy individuals. This R13 application is requesting funds to support the 8th ICGPP to be held October 9 -12, 2022 in Omaha, Nebraska. Our diverse organizing and scientific committee comprises ten principal investigators from various academic institutions representing the full range of medically relevant gram- positive bacteria. Although other meetings exist in the US that cover various aspects of bacterial pathogenesis or prokaryotic biology, this is the only meeting focused specifically on gram-positive pathogenesis and biology, and which provides a collegial and supportive environment that fosters interactions between established investigators and junior scientists. Young scientists have the option of presenting their research in either poster or oral format and, in 2018, out of the 27 non-keynote speakers, 17 trainees and 8 Assistant Professors gave oral research presentations. Four internationally known scientists have already agreed to give keynote presentations at the 2022 ICGPP: Drs. Andreas Peschel (University of Tubingen), Drusilla Burns (U.S. Food and Drug Administration), Shonna McBride (Emory University) and Jose Lemos (University of Florida). To keep registration fees low ...