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Full-Text Articles in Organisms

Cryptococcus Neoformans Melanization Incorporates Multiple Catecholamines To Produce Polytypic Melanin, Rosanna P. Baker, Christine Chrissian, Ruth E. Stark, Arturo Casadevall Dec 2021

Cryptococcus Neoformans Melanization Incorporates Multiple Catecholamines To Produce Polytypic Melanin, Rosanna P. Baker, Christine Chrissian, Ruth E. Stark, Arturo Casadevall

Publications and Research

Melanin is a major virulence factor in pathogenic fungi that enhances the ability of fungal cells to resist immune clearance. Cryptococcus neoformans is an important human pathogenic fungus that synthesizes melanin from exogenous tissue catecholamine precursors during infection, but the type of melanin made in cryptococcal meningoencephalitis is unknown. We analyzed the efficacy of various catecholamines found in brain tissue in supporting melanization using animal brain tissue and synthetic catecholamine mixtures reflecting brain tissue proportions. Solid-state NMR spectra of the melanin pigment produced from such mixtures yielded more melanin than expected if only the preferred constituent dopamine had been incorporated, …


The Temperature-Dependent Conformational Ensemble Of Sars-Cov-2 Main Protease (Mpro), Ali Ebrahim, Blake T. Riley, Desigan Kumaran, Babak Andi, Martin R. Fuchs, Sean Mcsweeney, Daniel A. Keedy Nov 2021

The Temperature-Dependent Conformational Ensemble Of Sars-Cov-2 Main Protease (Mpro), Ali Ebrahim, Blake T. Riley, Desigan Kumaran, Babak Andi, Martin R. Fuchs, Sean Mcsweeney, Daniel A. Keedy

Publications and Research

The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or Mpro, is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of Mpro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded Mpro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for Mpro, including …


Editorial: Pathogens, Pathobionts, And Autoimmunity, Linda A. Spatz, Gregg J. Silverman, Judith A. James Sep 2021

Editorial: Pathogens, Pathobionts, And Autoimmunity, Linda A. Spatz, Gregg J. Silverman, Judith A. James

Publications and Research

No abstract provided.


Telomeric And Sub-Telomeric Structure And Implications In Fungal Opportunistic Pathogens, Raffaella Diotti, Michelle Esposito, Chang Hui Shen Jun 2021

Telomeric And Sub-Telomeric Structure And Implications In Fungal Opportunistic Pathogens, Raffaella Diotti, Michelle Esposito, Chang Hui Shen

Publications and Research

Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity …


Intangible Cultural Heritage: A Benefit To Climate-Displaced And Host Communities, Gül Aktürk, Martha B. Lerski May 2021

Intangible Cultural Heritage: A Benefit To Climate-Displaced And Host Communities, Gül Aktürk, Martha B. Lerski

Publications and Research

Climate change is borderless, and its impacts are not shared equally by all communities. It causes an imbalance between people by creating a more desirable living environment for some societies while erasing settlements and shelters of some others. Due to floods, sea level rise, destructive storms, drought, and slow-onset factors such as salinization of water and soil, people lose their lands, homes, and natural resources. Catastrophic events force people to move voluntarily or involuntarily. The relocation of communities is a debatable climate adaptation measure which requires utmost care with human rights, ethics, and psychological well-being of individuals upon the issues …


When The Pandemic Opts For The Lockdown: Secretion System Evolution In The Cholera Bacterium, Francis J. Santoriello, Stefan Pukatzki Feb 2021

When The Pandemic Opts For The Lockdown: Secretion System Evolution In The Cholera Bacterium, Francis J. Santoriello, Stefan Pukatzki

Publications and Research

Vibrio cholerae, the causative agent of the diarrheal disease cholera, is a microbe capable of inhabiting two different ecosystems: chitinous surfaces in brackish, estuarine waters and the epithelial lining of the human gastrointestinal tract. V. cholerae defends against competitive microorganisms with a contact-dependent, contractile killing machine called the type VI secretion system (T6SS) in each of these niches. The T6SS resembles an inverted T4 bacteriophage tail and is used to deliver toxic effector proteins into neighboring cells. Pandemic strains of V. cholerae encode a unique set of T6SS effector proteins, which may play a role in pathogenesis or pandemic …


Biological Sex Influences Susceptibility To Acinetobacter Baumannii Pneumonia In Mice, Sílvia Pires, Adeline Peignier, Jeremy Seto, Davida S. Smyth, Dane Parker Apr 2020

Biological Sex Influences Susceptibility To Acinetobacter Baumannii Pneumonia In Mice, Sílvia Pires, Adeline Peignier, Jeremy Seto, Davida S. Smyth, Dane Parker

Publications and Research

Acinetobacter baumannii (A. baumannii) is an extremely versatile multidrug-resistant pathogen with a very high mortality rate; therefore, it has become crucial to understand the host response during its infection. Given the importance of mice for modeling infection and their role in preclinical drug development, equal emphasis should be placed on the use of both sexes. Through our studies using a murine model of acute pneumonia with A. baumannii, we observed that female mice were more susceptible to infection. Likewise, treatment of male mice with estradiol increased their susceptibility to infection. Analysis of the airway compartment revealed enhanced inflammation and reduced …


What We Do Not Know About Fungal Cell Adhesion Molecules, Peter N. Lipke May 2018

What We Do Not Know About Fungal Cell Adhesion Molecules, Peter N. Lipke

Publications and Research

There has been extensive research on structure and function of fungal cell adhesion molecules, but the most of the work has been about adhesins in Candida albicans and Saccharomyces cerevisiae. These yeasts are members of a single ascomycete order, and adhesion molecules from the six other fungal phyla are only sparsely described in the literature. In these other phyla, most of the research is at the cellular level, rather than at the molecular level, so there has been little characterization of the adhesion molecules themselves. A catalog of known adhesins shows some common features: high Ser/Thr content, tandem repeats, N- …


Anomaly Detection In Host Signaling Pathways For The Early Prognosis Of Acute Infection, Kun Wang, Stanley Langevin, Corey S. O'Hern, Mark D. Shattuck, Serenity Ogle, Adriana Forero, Juliet Morrison, Richard Slayden, Michael G. Katze, Michael Kirby Aug 2016

Anomaly Detection In Host Signaling Pathways For The Early Prognosis Of Acute Infection, Kun Wang, Stanley Langevin, Corey S. O'Hern, Mark D. Shattuck, Serenity Ogle, Adriana Forero, Juliet Morrison, Richard Slayden, Michael G. Katze, Michael Kirby

Publications and Research

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic …


Fungal Melanin: What Do We Know About Structure?, Joshua D. Nosanchuk, Ruth E. Stark, Arturo Casadevall Dec 2015

Fungal Melanin: What Do We Know About Structure?, Joshua D. Nosanchuk, Ruth E. Stark, Arturo Casadevall

Publications and Research

The production of melanin significantly enhances the virulence of many important human pathogenic fungi. Despite fungal melanin’s importance in human disease, as well as melanin’s contribution to the ability of fungi to survive in diverse hostile environments, the structure of melanin remains unsolved. Nevertheless, ongoing research efforts have progressively revealed several notable structural characteristics of this enigmatic pigment, which will be the focus of this review. These compositional and organizational insights could further our ability to develop novel therapeutic approaches to combat fungal disease and enhance our understanding of how melanin is inserted into the cell wall.


Phylogenomics Of Reichenowia Parasitica, An Alphaproteobacterial Endosymbiont Of The Freshwater Leech Placobdella Parasitica, Sebastian Kvist, Apurva Narechania, Alejandro Oceguera-Figueroa, Bella Fuks, Mark E. Siddall Nov 2011

Phylogenomics Of Reichenowia Parasitica, An Alphaproteobacterial Endosymbiont Of The Freshwater Leech Placobdella Parasitica, Sebastian Kvist, Apurva Narechania, Alejandro Oceguera-Figueroa, Bella Fuks, Mark E. Siddall

Publications and Research

Although several commensal alphaproteobacteria form close relationships with plant hosts where they aid in (e.g.,) nitrogen fixation and nodulation, only a few inhabit animal hosts. Among these, Reichenowia picta, R. ornata and R. parasitica, are currently the only known mutualistic, alphaproteobacterial endosymbionts to inhabit leeches. These bacteria are harbored in the epithelial cells of the mycetomal structures of their freshwater leech hosts, Placobdella spp., and these structures have no other obvious function than housing bacterial symbionts. However, the function of the bacterial symbionts has remained unclear. Here, we focused both on exploring the genomic makeup of R. parasitica and on …