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Full-Text Articles in Medicine and Health Sciences

Characterization Of The Paracoccidioides Hypoxia Response Reveals New Insights Into Pathogenesis Mechanisms Of This Important Human Pathogenic Fungus, Patrícia De Sousa Lima, Dawoon Chung, Alexandre Melo Bailão, Robert A. Cramer, Célia Maria De Almeida Soares Dec 2015

Characterization Of The Paracoccidioides Hypoxia Response Reveals New Insights Into Pathogenesis Mechanisms Of This Important Human Pathogenic Fungus, Patrícia De Sousa Lima, Dawoon Chung, Alexandre Melo Bailão, Robert A. Cramer, Célia Maria De Almeida Soares

Dartmouth Scholarship

Background: Hypoxic microenvironments are generated during fungal infection. It has been described that to survive in the human host, fungi must also tolerate and overcome in vivo microenvironmental stress conditions including low oxygen tension; however nothing is known how Paracoccidioides species respond to hypoxia. The genus Paracoccidioides comprises human thermal dimorphic fungi and are causative agents of paracoccidioidomycosis (PCM), an important mycosis in Latin America.


The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence By Enhancing Resistance To Neutrophil Extracellular Traps, Mark J. Lee, Hong Liu, Bridget M. Barker, Brendan D. Snarr, Fabrice M. Gravelat, Qusai Al Abdallah, Christina Gavino, Shane R. Baistrocchi, Hanna Ostapska, Tianli Xiao, Benjamin Ralph, Norma V. Solis, Melanie Lehoux, Stefanie D. Baptista, Arsa Thammahong Oct 2015

The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence By Enhancing Resistance To Neutrophil Extracellular Traps, Mark J. Lee, Hong Liu, Bridget M. Barker, Brendan D. Snarr, Fabrice M. Gravelat, Qusai Al Abdallah, Christina Gavino, Shane R. Baistrocchi, Hanna Ostapska, Tianli Xiao, Benjamin Ralph, Norma V. Solis, Melanie Lehoux, Stefanie D. Baptista, Arsa Thammahong

Dartmouth Scholarship

Of the over 250 Aspergillus species, Aspergillus fumigatus accounts for up to 80% of invasive human infections. A. fumigatus produces galactosaminogalactan (GAG), an exopolysaccharide composed of galactose and N-acetyl-galactosamine (GalNAc) that mediates adherence and is required for full virulence. Less pathogenic Aspergillus species were found to produce GAG with a lower GalNAc content than A. fumigatus and expressed minimal amounts of cell wall-bound GAG. Increasing the GalNAc content of GAG of the minimally pathogenic A. nidulans, either through overexpression of the A. nidulans epimerase UgeB or by heterologous expression of the A. fumigatus epimerase …


Mitochondrial Activity And Cyr1 Are Key Regulators Of Ras1 Activation Of C. Albicans Virulence Pathways, Nora Grahl, Elora G. Demers, Allia K. Lindsay, Colleen E. Harty, Sven D. Wilger, Amy E. Piispanen, Deborah A. Hogan Aug 2015

Mitochondrial Activity And Cyr1 Are Key Regulators Of Ras1 Activation Of C. Albicans Virulence Pathways, Nora Grahl, Elora G. Demers, Allia K. Lindsay, Colleen E. Harty, Sven D. Wilger, Amy E. Piispanen, Deborah A. Hogan

Dartmouth Scholarship

Candida albicans is both a major fungal pathogen and a member of the commensal human microflora. The morphological switch from yeast to hyphal growth is associated with disease and many environmental factors are known to influence the yeast-to-hyphae switch. The Ras1-Cyr1-PKA pathway is a major regulator of C. albicans morphogenesis as well as biofilm formation and white-opaque switching. Previous studies have shown that hyphal growth is strongly repressed by mitochondrial inhibitors. Here, we show that mitochondrial inhibitors strongly decreased Ras1 GTP-binding and activity in C. albicans and similar effects were observed in other Candida species. Consistent with there …


A Self-Lysis Pathway That Enhances The Virulence Of A Pathogenic Bacterium, Kirsty A. Mcfarland, Emily L. Dolben, Michele Leroux, Tracy K. Kambara, Kathryn Ramsey, Robin Kirkpatrick, Joseph Mougous, Deborah Hogan, Simon Dove Jul 2015

A Self-Lysis Pathway That Enhances The Virulence Of A Pathogenic Bacterium, Kirsty A. Mcfarland, Emily L. Dolben, Michele Leroux, Tracy K. Kambara, Kathryn Ramsey, Robin Kirkpatrick, Joseph Mougous, Deborah Hogan, Simon Dove

Dartmouth Scholarship

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of …


Nonreplicating, Cyst-Defective Type Ii Toxoplasma Gondii Vaccine Strains Stimulate Protective Immunity Against Acute And Chronic Infection, Barbara Andrea Fox, David J. Bzik May 2015

Nonreplicating, Cyst-Defective Type Ii Toxoplasma Gondii Vaccine Strains Stimulate Protective Immunity Against Acute And Chronic Infection, Barbara Andrea Fox, David J. Bzik

Dartmouth Scholarship

Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of …