I investigated effects of environmental change on disease, and effects of disease on ecosystems, using a freshwater zooplankton host and its fungal parasite. This research involved lake surveys, manipulative experiments, and mathematical models. My results indicate that ecosystem characteristics such as habitat structure, nutrient availability, and quality of a host’s resources (here, phytoplankton) can affect the spread of disease. For example, a survey of epidemics in lakes revealed direct and indirect links between habitat structure and epidemic size, where indirect connections were mediated by non-host species. Then, in a mesocosm experiment in a lake, manipulations of habitat structure and nutrient availability interactively affected the spread of disease, and nutrient enrichment increased densities of infected hosts. In a separate laboratory experiment, poor quality resources were shown to decrease parasite transmission rate by altering host foraging behavior. My experimental results also suggest that disease can affect ecosystems through effects on host densities and host traits. In the mesocosm experiment, the parasite indirectly increased abundance of algal resources by decreasing densities of the zooplankton host. Disease in the experimental zooplankton populations also impacted nutrient stoichiometry of algae, which could entail a parasite-mediated shift in food quality for grazers such as the host. Additionally, I showed that infection dramatically reduces host feeding rate, and used a dynamic epidemiological model to illustrate how this parasite-mediated trait change could affect densities of resources and hosts, as well as the spread of disease. I discuss the implications of these ecosystem–disease interactions in light of ongoing changes to habitat and nutrient regimes in freshwater ecosystems.

No description available.

<p dir="ltr"><i>Candida glabrata</i> is a member of the gut microbiota that can become an opportunistic pathogen under certain conditions. It is known for its inherent resistance to azole antifungal drugs and its ability to rapidly develop resistance during treatment. However, the regulatory mechanisms that enable this commensal organism to survive in low-oxygen environments, such as the gut, and to develop antifungal resistance when it becomes pathogenic, are not fully understood. In this study, we demonstrate for the first time the roles of two zinc cluster transcription factors in <i>C. glabrata</i>, Hap1A and Hap1B, in contributing to azole drug resistance in both laboratory strains and drug-resistant clinical isolates, adaptation to hypoxia, and resistance to other antifungal drugs like polyenes and echinocandins under specific conditions.</p><p dir="ltr">Azole drugs, which target the Erg11 protein, are widely used to treat <i>Candida</i> infections. The regulation of azole-induced <i>ERG</i> gene expression and activation of drug efflux pumps in <i>C. glabrata</i> has primarily been linked to the zinc cluster transcription factors Upc2A and Pdr1. Here, we investigated the roles of <i>S. cerevisiae</i> Hap1 orthologs, Hap1A and Hap1B, in <i>C. glabrata</i> as direct regulators of <i>ERG</i> genes upon azole exposure.</p><p dir="ltr">Our research shows that deleting <i>HAP1</i> in the yeast model <i>S. cerevisiae</i> increases sensitivity to fluconazole due to the failure to induce <i>ERG11 </i>expression in the <i>hap1Δ</i> mutant compared to the wild-type strain. Although <i>C. glabrata</i> is closely related to <i>S. cerevisiae</i>, a whole genome duplication (WGD) event allowed <i>C. glabrata</i> to retain two HAP1 ohnologs, while <i>S. cerevisiae</i> lost one copy. Through phylogenetic and syntenic analyses, we identified Hap1A and Hap1B in <i>C. glabrata</i> as ohnologs of Hap1 in <i>S. cerevisiae</i>, which is known to regulate <i>ERG</i> gene expression under both aerobic and hypoxic conditions. Interestingly, deleting <i>HAP1B</i> in <i>C. glabrata</i> increased sensitivity to both triazole and imidazole drugs, similar to Hap1 in <i>S. cerevisiae</i>, while deleting <i>HAP1A </i>did not affect azole sensitivity.</p><p dir="ltr">Gene expression analysis revealed that the increased azole sensitivity in the <i>hap1BΔ </i>strain was due to reduced azole-induced <i>ERG</i> gene expression, leading to lower total endogenous ergosterol levels. Additionally, the loss of <i>HAP1B</i> in <i>C. glabrata</i> clinical isolates like SM1 and BG2, as well as in drug-resistant strains like SM3, also led to increased azole hypersusceptibility. While it was already known that losing <i>UPC2A</i> in <i>C. glabrata</i> increases azole sensitivity, our study is the first to demonstrate that the combined loss of both <i>HAP1B </i>and <i>UPC2A</i> makes <i>C. glabrata</i> strains even more sensitive to azoles than losing either gene alone. Additionally, we show that the loss of both <i>HAP1B </i>and the H3K4 histone methyltransferase <i>SET1</i> increases azole hypersensitivity more than the loss of either gene alone.</p><p dir="ltr">Interestingly, the Hap1A protein is barely detectable under aerobic conditions but is specifically induced under hypoxia, where it plays a crucial role in repressing <i>ERG</i> genes. In the absence of Hap1A, Hap1B compensates by acting as a transcriptional repressor. Our RNA sequencing analysis further showed that losing both <i>HAP1A</i> and <i>HAP1B</i> not only affects genes in the ergosterol biosynthesis pathway but also upregulates iron transport-related genes <i>FET3 </i>and <i>FTR1</i>. Moreover, we found that the hypoxic growth defect caused by the loss of both <i>HAP1A</i> and <i>HAP1B</i> is exacerbated when treated with the echinocandin caspofungin and the cell wall-damaging agent calcofluor white, indicating that these Hap1 ohnologs contribute to maintaining cell wall integrity under hypoxic conditions. Since <i>HAP1A</i> transcript levels remain stable under aerobic conditions, we suspect that Hap1A expression is regulated post-transcriptionally.</p><p dir="ltr">Furthermore, we discovered that the simultaneous loss of both HAP1A and HAP1B leads to increased hypersensitivity to the polyene antifungal drug amphotericin B, though the exact mechanism behind this phenotype remains unclear. Altogether, our study is the first to show that Hap1A and Hap1B have evolved distinct roles, enabling <i>C. glabrata</i> to adapt to specific host and environmental conditions.</p>

El moteado del níspero, causado por el hongo Fusicladium eriobotryae es la principal enfermedad que afecta al cultivo del níspero, produciendo pérdidas importantes en la cosecha en los años con condiciones climáticas adecuadas. Sin embargo, no existen estudios sobre la epidemiología y el control de esta enfermedad, por lo que éstos constituyen el principal objetivo de la presente Tesis. Para ello, se va ha caracterizar in vitro y en campo la influencia de las principales variables climáticas en el desarrollo de F. eriobotryae, desarrollándose ecuaciones matemáticas que modelicen esta relación. Por otro lado, se va a llevar a cabo un modelo epidemiológico para el moteado del níspero capaz de predecir, en función de las principales variables climáticas el riesgo de infección. Además, se realizará un estudio del control de la enfermedad que comprenderá, por un lado, la evaluación in vitro y en planta de la efectividad de las principales materias activas utilizadas para el control del moteado del níspero, y por otro la evaluación del grado de resistencia de una colección de aislados de F. eriobotryae a DMI y Metil-Tiofanato y la caracterización molecular de la misma. / González Domínguez, E. (2014). Biology, epidemiology and control of Fusicladium eriobotryae, causal agent of loquat scab [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/38715