Featured Publications
Abstract:
The contributions of commensal fungi to human health and disease are not well understood. Candida species such as C. albicans and C. glabrata are opportunistic pathogenic fungi and common colonizers of the human intestinal tract. They have been shown to affect the host immune system and interact with the gut microbiome and pathogenic microorganisms. Therefore, Candida species could be expected to play important ecological roles in the host gastrointestinal tract. Previously, our group demonstrated that pre-colonization of mice with C. albicans protected them against lethal C. difficile infection (CDI). Here we show that mice pre-colonized with C. glabrata succumbed to CDI more rapidly than mice that were not pre-colonized suggesting an enhancement in C. difficile pathogenesis. Further, when C. difficile was added to pre-formed C. glabrata biofilms, an increase in matrix and overall biomass was observed. These effects were also shown with C. glabrata clinical isolates. Interestingly, the presence of C. difficile increased C. glabrata biofilm susceptibility to caspofungin, indicating potential effects on the fungal cell wall. Defining this intricate and intimate relationship will lead to an understanding of the role of Candida species in the context of CDI and novel aspects of Candida biology.
The contributions of commensal fungi to human health and disease are not well understood. Candida species such as C. albicans and C. glabrata are opportunistic pathogenic fungi and common colonizers of the human intestinal tract. They have been shown to affect the host immune system and interact with the gut microbiome and pathogenic microorganisms. Therefore, Candida species could be expected to play important ecological roles in the host gastrointestinal tract. Previously, our group demonstrated that pre-colonization of mice with C. albicans protected them against lethal C. difficile infection (CDI). Here we show that mice pre-colonized with C. glabrata succumbed to CDI more rapidly than mice that were not pre-colonized suggesting an enhancement in C. difficile pathogenesis. Further, when C. difficile was added to pre-formed C. glabrata biofilms, an increase in matrix and overall biomass was observed. These effects were also shown with C. glabrata clinical isolates. Interestingly, the presence of C. difficile increased C. glabrata biofilm susceptibility to caspofungin, indicating potential effects on the fungal cell wall. Defining this intricate and intimate relationship will lead to an understanding of the role of Candida species in the context of CDI and novel aspects of Candida biology.
Abstract:
Virtually all Candida species linked to clinical candidiasis are capable of forming highly resistant biofilms on
different types of surfaces, which poses an additional significant threat and further complicates therapy of these infections. There is a scarcity of antifungal agents, and their effectiveness, particularly against biofilms, is limited. Here we provide a historical perspective on antifungal agents and therapy of Candida biofilms. As we reflect upon the past, consider the present, and look towards the future of antifungal therapy of Candida biofilms, we believe that there are reasons to remain optimistic, and that the major challenges of Candida biofilm therapy can be conquered within a reasonable timeframe.
Virtually all Candida species linked to clinical candidiasis are capable of forming highly resistant biofilms on
different types of surfaces, which poses an additional significant threat and further complicates therapy of these infections. There is a scarcity of antifungal agents, and their effectiveness, particularly against biofilms, is limited. Here we provide a historical perspective on antifungal agents and therapy of Candida biofilms. As we reflect upon the past, consider the present, and look towards the future of antifungal therapy of Candida biofilms, we believe that there are reasons to remain optimistic, and that the major challenges of Candida biofilm therapy can be conquered within a reasonable timeframe.
Abstract:
Scientific contributions by members from historically marginalized communities (HMCs) have been largely ignored, uncredited, and in some cases erased from history. This has contributed to science, technology, engineering, and math (STEM) curricula lacking diversity. In this study, we present an Honors seminar course aimed to highlight the discoveries of scientists from HMCs, centered around reading primary literature in a way that builds our students' research skills. The course provides students with opportunities for active learning, skill building, and mentorship that are key for persistence of students in the STEM “leaky pipeline.” Students also read biographies of scientists from HMCs, interact with guest speakers, and choose scientists to highlight (in final papers and presentations) and publicize (through the creation of Wikipedia pages). Additionally, students use community-building methodologies to build a safe classroom and gain tools to have conversations about diversity, inequities, and intersectionality in STEM. In self-reporting surveys, 93.7% of students strongly agreed that their appreciation for marginalized scientists increased and 92.6% reported that the course met very well the goal of refining their research skills. These findings support the effectiveness of this novel course. We provide two lists (one of 137 scientists and one of 57 scientist biographies) that will allow faculty teaching a wide range of science classes to select examples of scientists and discoveries to highlight in their courses. This course represents a novel platform to diversify STEM curricula while engaging and empowering students from historically marginalized communities.
Scientific contributions by members from historically marginalized communities (HMCs) have been largely ignored, uncredited, and in some cases erased from history. This has contributed to science, technology, engineering, and math (STEM) curricula lacking diversity. In this study, we present an Honors seminar course aimed to highlight the discoveries of scientists from HMCs, centered around reading primary literature in a way that builds our students' research skills. The course provides students with opportunities for active learning, skill building, and mentorship that are key for persistence of students in the STEM “leaky pipeline.” Students also read biographies of scientists from HMCs, interact with guest speakers, and choose scientists to highlight (in final papers and presentations) and publicize (through the creation of Wikipedia pages). Additionally, students use community-building methodologies to build a safe classroom and gain tools to have conversations about diversity, inequities, and intersectionality in STEM. In self-reporting surveys, 93.7% of students strongly agreed that their appreciation for marginalized scientists increased and 92.6% reported that the course met very well the goal of refining their research skills. These findings support the effectiveness of this novel course. We provide two lists (one of 137 scientists and one of 57 scientist biographies) that will allow faculty teaching a wide range of science classes to select examples of scientists and discoveries to highlight in their courses. This course represents a novel platform to diversify STEM curricula while engaging and empowering students from historically marginalized communities.
Characterization of the Effects of Candida Gastrointestinal Colonization on Clostridioides difficile Infection in a Murine Model
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Abstract:
The role of fungal colonizers of the gastrointestinal tract during disease states is not well understood.
Antibiotic treatment renders patients highly susceptible to infection by the bacterial pathogen C. difficile
while also leading to blooms in fungal commensals, setting the stage for trans-kingdom interactions. Here,
we describe a murine model of Candida gastrointestinal colonization coupled to a C. difficile infection
(CDI) model, the measurement of CFU of both organisms, and collection of cecum and colon contents for
the purpose of quantifying C. difficile toxin production. Additionally, we describe how to induce and purify
C. difficile spores.
The role of fungal colonizers of the gastrointestinal tract during disease states is not well understood.
Antibiotic treatment renders patients highly susceptible to infection by the bacterial pathogen C. difficile
while also leading to blooms in fungal commensals, setting the stage for trans-kingdom interactions. Here,
we describe a murine model of Candida gastrointestinal colonization coupled to a C. difficile infection
(CDI) model, the measurement of CFU of both organisms, and collection of cecum and colon contents for
the purpose of quantifying C. difficile toxin production. Additionally, we describe how to induce and purify
C. difficile spores.
Abstract:
Prior antibiotic treatment is a risk factor for Clostridioides difficile infection (CDI); the commensal gut microbiota plays a key role in determining host susceptibility to the disease. Previous studies demonstrate that the pre-colonization of mice with a commensal fungus, Candida albicans, protects against a lethal challenge with C. difficile spores. The results reported here demonstrate that the cecum contents of antibiotic-treated mice with C. albicans colonization contained different levels of several lipid species, including non-esterified, unsaturated long-chain fatty acids compared to non-C. albicans-colonized mice. Mice fed olive oil for one week and challenged with C. difficile spores showed enhanced survival compared to PBS-fed mice. The amount of olive oil administered was not sufficient to cause weight gain or to result in significant changes to the bacterial microbiota, in contrast to the effects of a high-fat diet. Furthermore, the direct exposure of C. difficile bacteria in laboratory culture to the unsaturated fatty acid oleic acid, the major fatty acid found in olive oil, reduced the transcription of genes encoding the toxins and reduced the survival of bacteria in the post-exponential phase. Therefore, the effects of C. albicans on the metabolite milieu contributed to the attenuation of C. difficile virulence.
Prior antibiotic treatment is a risk factor for Clostridioides difficile infection (CDI); the commensal gut microbiota plays a key role in determining host susceptibility to the disease. Previous studies demonstrate that the pre-colonization of mice with a commensal fungus, Candida albicans, protects against a lethal challenge with C. difficile spores. The results reported here demonstrate that the cecum contents of antibiotic-treated mice with C. albicans colonization contained different levels of several lipid species, including non-esterified, unsaturated long-chain fatty acids compared to non-C. albicans-colonized mice. Mice fed olive oil for one week and challenged with C. difficile spores showed enhanced survival compared to PBS-fed mice. The amount of olive oil administered was not sufficient to cause weight gain or to result in significant changes to the bacterial microbiota, in contrast to the effects of a high-fat diet. Furthermore, the direct exposure of C. difficile bacteria in laboratory culture to the unsaturated fatty acid oleic acid, the major fatty acid found in olive oil, reduced the transcription of genes encoding the toxins and reduced the survival of bacteria in the post-exponential phase. Therefore, the effects of C. albicans on the metabolite milieu contributed to the attenuation of C. difficile virulence.