Kah&Mac lab

Home        Lab Members        Get Involved        Protocols        Resources        News        Schedule        Publications        Contact       

Welcome to the Fisher Lab Wiki We combine a diverse suite of genetic, biochemical, molecular, and genomic approaches with a variety of high-throughput host systems to address fundamental questions concerning how soil bacteria impact human health and agriculture. Ecologic Basis of Opportunistic Virulence Non-commensal opportunistic bacterial pathogens are highly adapted to success in soil niches. This contrasts with commensal opportunistic pathogens and obligate pathogens of mammals and humans, which share a long co-evolutionary history with their hosts. How then are soil microbes, which are unlikely to ever encounter a mammal, able to cause infection upon accidental inoculation into a host? We hypothesize that defense mechanisms geared toward surviving ecological stresses, such as antimicrobial exudates secreted by plants, fungi and other bacteria or predation by bacterivorous protists, are activated when these organisms are confronted by the innate immune system. We are using functional genomics approaches and a wide variety of ecologically-focused screening assays to characterize loci that facilitate resistance to these stresses and are linking back from there to the role these same systems play in disease. In situ Biofilm formation by Opportunistic Pathogens Colonization usually precedes infection by non-commensal opportunistic pathogens. Despite the knowledge that biofilms formed on specific surfaces and in specific micro-environments exhibit distinct physiologic profiles, the majority of scientific studies aimed at understanding colonization model biofilm formation in vitro - usually in 96-well polystyrene microtiter plates. We are building a model system whereby clinically relevant surfaces (e.g.; venous catheters) can be implanted into the hemolymph of cockroaches before or after seeding with a pathogen of interest, thereby allowing us to examine the process of biofilm formation in an environment that is physiologically similar to mammalian blood and includes pressure from the innate immune system. The images at the top of this page are a series of SEMs of S. maltophilia biofilms formed on a teflon catheter implanted into the hemolymph of a Blaptica dubia cockroach. Virulence Priming in Opportunistic Pathogens As environmentally resident opportunistic pathogens transverse ecological, spacial, and temporal barriers prior to inoculation into a human host, they encounter myriad physiologic stressors. We are attempting to understand both how these organisms survive these stresses and how these stresses may enhance or modify the physiologic state of the organism-ultimately leading to a more infectious or virulent phenotype. Currently, our work in this area focuses on S. maltophilia and Listeria monocytogenes, two clinically important environmentally resident opportunistic pathogens. Germination and Early-stage Pathogenesis of Paenibacillus larvae P. larvae is the etiologic agent of American Foulbrood disease of honeybees, a disease of great agricultural impact. Currently, no viable treatment options exist and infected colonies must be destroyed at great cost to an industry already under tremendous pressure to maintain the necessary number of colonies nationwide. It is our hope that by understanding early-stage pathogenesis, we can develop treatments that will rescue an infected colony and prevent spread to neighboring hives. Agricultural Probiotics We are currently examining how certain soil bacteria can enhance plant growth and production with special emphasis on how they may protect from disease. Invertebrate "Models" (I prefer the term "assays") In the course of our studies, we have compiled considerable expertise in a number of popular invertebrate systems. These include Dictyostelium amoeba, Tetrahymena, C. elegans, duckweek (L. minor), a number of insects including wax worms (G. melonella) and cockroaches (B. dubia), and tissue culture systems. Join Us We are highly collaborative, please contact us if you are interested in working together. We are always in need of motivated and talented students, please submit inquiries via the contact tab.