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(Virulence Priming of Opportunistic Pathogens)
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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.  <br>
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.  <br>
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==== '''Colonization and Innate Immune Evasion by the Emerging Opportunistic Pathogen ''Stenotrophomonas maltophilia'' '''====
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====Ecologic Basis of Opportunistic Virulence====
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''S. maltophilia'' is an emerging, multi-drug-resistant (MDR), opportunistic pathogen that frequently colonizes ventilator tubes and indwelling medical devices where it forms biofilms. Initial colonization can lead to severe, life-threatening infection and recent studies show that both incidence and prevalence are increasing, especially in immunocompromised, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and cancer patients—demographic groups key to the research
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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 systemWe are using functional genomics approaches to characterize loci that facilitate resistance to these stresses and are linking back from there to the role these same systems play in disease.<br>
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mission of the National Institutes of Health (NIH; Brook, 2012; Emerson et al., 2010; Metan et al., 2006). Currently, there are critical knowledge gaps with respect to how ''S. maltophilia'' avoids clearance by humoral and cellular components of the immune system and how biofilm communities are established ''in vivo''.  We are using a variety of forward genetic screens to identify bacterial factors involved in colonization of biotic and abiotic surfaces, host cell toxicity, and immune evasion.<br>
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====''In situ'' Biofilm formation by Opportunistic Pathogens====
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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.<br>
====Virulence Priming in Opportunistic Pathogens====
====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.<br>
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.<br>
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====Invertebrate Assays of Bacterial Virulence====
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====Germination and Early-stage Pathogenesis of ''Paenibacillus larvae''====
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''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.<br>
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====Agricultural Probiotics====
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We are currently examining how certain soil bacteria can enhance plant growth and production with special emphasis on how they may protect from disease.
====Join Us====
====Join Us====
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We are always interested in motivated students, please submit inquiries via the contact tab. <br>
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We are highly collaborative, please contact us if you are interested in working together.
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We are always in need of motivated and talented students, please submit inquiries via the contact tab. <br>
[[Category:Lab]]
[[Category:Lab]]

Revision as of 11:56, 30 April 2014

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Contents

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 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.

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.

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