Browsing by Author "Kontoyiannis, Dimitrios P."

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    EGF-mediated suppression of cell extrusion during mucosal damage attenuates opportunistic fungal invasion
    (Cell Press, 2021) Wurster, Sebastian; Ruiz, Oscar E.; Samms, Krystin M.; Tatara, Alexander M.; Albert, Nathaniel D.; Kahan, Philip H.; Nguyen, Anh Trinh; Mikos, Antonios G.; Kontoyiannis, Dimitrios P.; Eisenhoffer, George T.
    Severe and often fatal opportunistic fungal infections arise frequently following mucosal damage caused by trauma or cytotoxic chemotherapy. Interaction of fungal pathogens with epithelial cells that comprise mucosae is a key early event associated with invasion, and, therefore, enhancing epithelial defense mechanisms may mitigate infection. Here, we establish a model of mold and yeast infection mediated by inducible epithelial cell loss in larval zebrafish. Epithelial cell loss by extrusion promotes exposure of laminin associated with increased fungal attachment, invasion, and larval lethality, whereas fungi defective in adherence or filamentation have reduced virulence. Transcriptional profiling identifies significant upregulation of the epidermal growth factor receptor ligand epigen (EPGN) upon mucosal damage. Treatment with recombinant human EPGN suppresses epithelial cell extrusion, leading to reduced fungal invasion and significantly enhanced survival. These data support the concept of augmenting epithelial restorative capacity to attenuate pathogenic invasion of fungi associated with human disease.
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    Factors affecting patient outcome in primary cutaneous aspergillosis
    (Wolters Kluwer, 2016) Tatara, Alexander M.; Mikos, Antonios G.; Kontoyiannis, Dimitrios P.
    Primary cutaneous aspergillosis (PCA) is an uncommon infection of the skin. There is a paucity of organized literature regarding this entity in regard to patient characteristics, associated Aspergillus species, and treatment modalities on outcome (disease recurrence, disease dissemination, and mortality). We reviewed all published reports of PCA from 1967 to 2015. Cases were deemed eligible if they included the following: patient baseline characteristics (age, sex, underlying condition), evidence of proven or probable PCA, primary treatment strategy, and outcome. We identified 130 eligible cases reported from 1967 to 2015. The patients were predominantly male (63.8%) with a mean age of 30.4 ± 22.1 years. Rates of PCA recurrence, dissemination, and mortality were 10.8%, 18.5%, and 31.5%, respectively. In half of the cases, there was an association with a foreign body. Seven different Aspergillus species were reported to cause PCA. Systemic antifungal therapy without surgery was the most common form of therapy (60% of cases). Disease dissemination was more common in patients with underlying systemic conditions and occurred on average 41.4 days after PCA diagnosis (range of 3–120 days). In a multivariate linear regression model of mortality including only patients with immunosuppressive conditions, dissemination and human immunodeficiency virus/acquired immune deficiency syndrome were statistically significantly associated with increased mortality. Nearly one-third of patients with PCA die with the disease. Dissemination and host status are critical in patient outcome.
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    Poly(diol fumarates) and poly(diol fumarate-co-succinates)
    (2020-11-17) Tatara, Alexander Mitchell; Watson, Emma; Mikos, Antonios G.; Kontoyiannis, Dimitrios P.; Rice University; Board of Regents, The University of Texas System; United States Patent and Trademark Office
    The disclosure relates to a class of diol-based, unsaturated aliphatic polyesters that biodegrade into monomers capable of mitigating infection. These poly(diol fumarates) (PDFs) and poly(diol fumarate-co-succinates) (PDFSs), can be crosslinked to form networks of scaffolds with antimicrobial degradation products. Both the diol carbon length and the degree of available double bonds are tunable, resulting in a highly controllable class of antimicrobial polymers useful for cell scaffolds and drug delivery systems and devices.