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Full-Text Articles in Fungi

289— Phenotypic Characterization Of Neurospora Crassa Fsd-1 Overexpression Strains, Hannah Smith Apr 2021

289— Phenotypic Characterization Of Neurospora Crassa Fsd-1 Overexpression Strains, Hannah Smith

GREAT Day

Neurospora crassa is a model filamentous fungal organism that can reproduce both asexually and sexually. Little is known about the molecular mechanisms that regulate the N. crassa female sexual development cycle. The transcription factor fsd-1 is necessary for sexual development, and fsd-1 deletion strains show delayed development of female reproductive structures and are sterile. Through previous experiments, we have been able to determine that there are three different transcripts of the fsd-1 gene, which differ by the length and intron/exon structure of their 5’ untranslated region. This project focuses on phenotypically characterizing the reproductive ability of strains overexpressing fsd-1 ...


Microbiological Study In A Gneissic Cave From Sri Lanka, With Special Focus On Potential Antimicrobial Activities, Ethige Isuru P. Silva, Pathmakumara Jayasingha, Saman Senanayake, Anura Dandeniya, Dona Helani Munasinghe Mar 2021

Microbiological Study In A Gneissic Cave From Sri Lanka, With Special Focus On Potential Antimicrobial Activities, Ethige Isuru P. Silva, Pathmakumara Jayasingha, Saman Senanayake, Anura Dandeniya, Dona Helani Munasinghe

International Journal of Speleology

The emergence of antibiotic resistance is a global health crisis, thus the search for novel antimicrobial compounds has become a continuous necessity. Underexplored and extreme environments, such as cave ecosystems, have been identified as a promising potential source for the discovery of novel microorganisms with novel antimicrobial compounds (AMC). This study presents the first cave microbiological investigation in Sri Lanka, with a special preference for bioprospecting of novel AMC. The cave sediment characterization demonstrated the presence of close to strong acidic conditions (pH 3.1 – 3.3) and thus indicates the possibility of isolating acidophilic microorganisms. Eight cave wall/ceiling ...


Swi/Snf Senses Carbon Starvation With A Ph-Sensitive Low Complexity Sequence [Preprint], J. Ignacio Gutiérrez, Gregory P. Brittingham, Yonca Karadeniz, Kathleen D. Tran, Arnob Dutta, Alex S. Holehouse, Craig L. Peterson, Liam J. Holt Mar 2021

Swi/Snf Senses Carbon Starvation With A Ph-Sensitive Low Complexity Sequence [Preprint], J. Ignacio Gutiérrez, Gregory P. Brittingham, Yonca Karadeniz, Kathleen D. Tran, Arnob Dutta, Alex S. Holehouse, Craig L. Peterson, Liam J. Holt

University of Massachusetts Medical School Faculty Publications

It is increasingly appreciated that intracellular pH changes are important biological signals. This motivates the elucidation of molecular mechanisms of pH-sensing. We determined that a nucleocytoplasmic pH oscillation was required for the transcriptional response to carbon starvation in S. cerevisiae. The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. We found that a glutamine-rich low complexity sequence (QLC) in the SNF5 subunit of this complex, and histidines within this sequence, were required for efficient transcriptional reprogramming during carbon starvation. Furthermore, the SNF5 QLC mediated pH-dependent recruitment of SWI/SNF to a model promoter in vitro ...


All You Need To Know And More About The Diagnosis And Management Of Rare Mold Infections, Martin Hoenigl, Stuart M. Levitz, Audrey N. Schuetz, Sean X. Zhang, Oliver A. Cornely Feb 2021

All You Need To Know And More About The Diagnosis And Management Of Rare Mold Infections, Martin Hoenigl, Stuart M. Levitz, Audrey N. Schuetz, Sean X. Zhang, Oliver A. Cornely

Open Access Publications by UMMS Authors

Invasive mold infections caused by molds other than Aspergillus spp. or Mucorales are emerging. The reported prevalences of infection due to these rare fungal pathogens vary among geographic regions, driven by differences in climatic conditions, susceptible hosts, and diagnostic capabilities. These rare molds-Fusarium, Lomentospora, and Scedosporium species and others-are difficult to detect and often show intrinsic antifungal resistance. Now, international societies of medical mycology and microbiology have joined forces and created the "Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human ...


Sociodemographic, Clinical Characteristics, And Outcomes Of Influenza Pneumonia Patients Admitted In A Tertiary Care Hospital In Karachi, Pakistan: Findings From A Cross-Sectional Study, Fazal Ur Rehman, Muhammad Arslan Ahmed, Kashif Aziz, Mahmooda Jabeen Ashraf, Tazein Amber, Sumera Aziz Ali Feb 2021

Sociodemographic, Clinical Characteristics, And Outcomes Of Influenza Pneumonia Patients Admitted In A Tertiary Care Hospital In Karachi, Pakistan: Findings From A Cross-Sectional Study, Fazal Ur Rehman, Muhammad Arslan Ahmed, Kashif Aziz, Mahmooda Jabeen Ashraf, Tazein Amber, Sumera Aziz Ali

Section of Internal Medicine

Objective: To determine the sociodemographic, clinical characteristics, and outcomes of influenza pneumonia patients in tertiary care hospital, Karachi Pakistan.
Study design: A cross-sectional study.
Place and duration of study: The Aga Khan University Hospital Karachi Pakistan from January 2013 to December 2018. Methodology: All adult patients who were older than 18 years and suspected to have viral pneumonia were included in the study. Data were abstracted on 105 patients and were entered on preformed proforma after reviewing the files of patients.
Results: Ninety-four (89.5%) patients were influenza positive and 15.2% (n=16) had been vaccinated. Around 92.4 ...


Covid-19 Presenting With Spontaneous Pneumothorax, Intisar Ahmed, Hunaina Shahab, Muhammad Arslan Ahmed, Muhammad Sohaib Jan 2021

Covid-19 Presenting With Spontaneous Pneumothorax, Intisar Ahmed, Hunaina Shahab, Muhammad Arslan Ahmed, Muhammad Sohaib

Section of Cardiology

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease mainly affects respiratory system. Its common clinical findings include fever, cough and shortness of breath. Characteristic radiological features of the disease include peripherally distributed, bilateral ground-glass opacities, predominantly involving the lower lung zones. In this report, we present a case of COVID-19 disease presenting with spontaneous pneumothorax. A 26-year male patient was admitted to the Emergency Department with fever, dry cough, shortness of breath and right-sided chest pain. Radiographic imaging of the patient revealed pneumothorax on the right and peripherally distributed non-homogenous opacification ...


Chytridiomycota In Tree Bark, Paige Strasko Dec 2020

Chytridiomycota In Tree Bark, Paige Strasko

Honors College

Chytridiomycota is a phylum of microscopic aquatic fungi that form motile spores that typically have a single posterior flagellum, thus they require water to disperse (James et al., 2000). Chytridiomycota, collectively called chytrids, have round shapes with structures called rhizoids that absorb nutrients and anchor them to their substrate (Mueller et al., 2004). Chytrids are typically found in aquatic environments and soils since zoospores require water to germinate (James et al., 2000), but they also have been found in a number of unexpected environments. Chytrids are difficult to find because they are microscopic and have time-sensitive life cycles (Mueller et ...


Dormancy-To-Death Transition In Yeast Spores Occurs Due To Gradual Loss Of Gene-Expressing Ability, Theo Maire, Tim Allertz, Max A. Betjes, Hyun Youk Nov 2020

Dormancy-To-Death Transition In Yeast Spores Occurs Due To Gradual Loss Of Gene-Expressing Ability, Theo Maire, Tim Allertz, Max A. Betjes, Hyun Youk

Open Access Publications by UMMS Authors

Dormancy is colloquially considered as extending lifespan by being still. Starved yeasts form dormant spores that wake-up (germinate) when nutrients reappear but cannot germinate (die) after some time. What sets their lifespans and how they age are open questions because what processes occur-and by how much-within each dormant spore remains unclear. With single-cell-level measurements, we discovered how dormant yeast spores age and die: spores have a quantifiable gene-expressing ability during dormancy that decreases over days to months until it vanishes, causing death. Specifically, each spore has a different probability of germinating that decreases because its ability to-without nutrients-express genes decreases ...


Invasive Pulmonary Infection By Syncephalastrum Species: Two Case Reports And Review Of Literature, Memoona Irshad, Nosheen Nasir, Urooj Haider Hashmi, Joveria Farooqi, Syed Faisal Mahmood Jul 2020

Invasive Pulmonary Infection By Syncephalastrum Species: Two Case Reports And Review Of Literature, Memoona Irshad, Nosheen Nasir, Urooj Haider Hashmi, Joveria Farooqi, Syed Faisal Mahmood

Section of Internal Medicine

Background: Syncephalastrum species belong to the class Zygomycetes and order Mucorale. These are found in the environment and tropical soil, usually presenting as colonizers and rarely cause human infection. Syncephalastrum racemosum is a species of the genus Syncephalastrum and is the most commonly identified pathogen. Most cases are reported in immunocompromised individuals, such as patients on long term steroids, poorly controlled diabetes, or patients with malignancy.
Case presentation: We are describing two cases of rare fungal infection by Syncephalastrum species causing invasive pulmonary manifestation. Both patients had compromised immune status and presented with worsening dyspnea to the emergency room. Both ...


Trichosporon Species And Fusarium Species As A Cause Of Empyema Thoracis In A Diabetic Patient, Nousheen Iqbal, Muhammad Ammar, Muhammad Irfan, Kauser Jabeen Jul 2020

Trichosporon Species And Fusarium Species As A Cause Of Empyema Thoracis In A Diabetic Patient, Nousheen Iqbal, Muhammad Ammar, Muhammad Irfan, Kauser Jabeen

Section of Pulmonary & Critical Care

Of late, fungal infections are increasingly being recognized in diabetic patients. Here we present a case of polymicrobial fungal empyema due to Trichosporon species and Fusarium species developed after community-acquired pneumonia in a diabetic patient. Trichosporon species are basidiomycetous yeast and Fusarium species are soil saprophytes with a worldwide distribution. Fungal empyema cases are rare and are mostly caused by Aspergillus and Candida species. Polymicrobial fungal empyema with Trichosporon species and Fusarium species has not been reported previously. Our patient was successfully treated with antifungal therapy. This case highlights that fungal empyema should be considered in diabetic patients especially if ...


The Discovery Of Metarhizium Anisopliae (Metchnikoff) Sorokin Isolates From Arkansas And Their Pathogenicity To Amblyomma Americanum L., Austin Goldsmith May 2020

The Discovery Of Metarhizium Anisopliae (Metchnikoff) Sorokin Isolates From Arkansas And Their Pathogenicity To Amblyomma Americanum L., Austin Goldsmith

Theses and Dissertations

The lone star tick Amblyomma americanum L. is the most abundant tick in Arkansas and has been implicated as a vector of many important disease-causing pathogens. Many species of entomopathogenic fungi have been isolated from several species of ticks, with some of these fungi being utilized for tick biocontrol. However, few studies have assessed the pathogenicity of entomopathogenic fungi to A. americanum. The objectives of this study were to: isolate and identify native Arkansas isolates of entomopathogenic fungi from wild A. americanum ticks exposed to soil and to compare the pathogenicity of one isolate (Metarhizium anisopliae (Metchnikoff) Sorokin isolate Savoy ...


The Effect Of Alcaligenes Faecalis On Inhibition Of Candida Albicans Biofilm And Planktonic Growth, Nausheen A. Siddiqui May 2020

The Effect Of Alcaligenes Faecalis On Inhibition Of Candida Albicans Biofilm And Planktonic Growth, Nausheen A. Siddiqui

Undergraduate Honors Theses

Candida albicans is a fungal microorganism found on the human body and in the environment. An opportunistic pathogen causing local and systemic infection, this fungus is one of the leading causes of nosocomial infections. More alarming is its growing resistance against the limited number of antifungals we have for treatment Candida infections. An area of current research, termed polymicrobial interactions, focuses on how different microorganisms interact with each other for limited space, nutrients, and survival. The current study focuses on attempting to inhibit planktonic and biofilm growth stages by using the benign bacterium Alcaligenes faecalis, previously shown in our lab ...


The Effects Of Farnesol, A Quorum Sensing Molecule From Candida Albicans, On Alcaligenes Faecalis, Savannah Hutson May 2020

The Effects Of Farnesol, A Quorum Sensing Molecule From Candida Albicans, On Alcaligenes Faecalis, Savannah Hutson

Undergraduate Honors Theses

Quorum sensing molecules have become a recent focus of study to learn if and how they can be used, both on their own and in conjecture with current antimicrobial methods, as a means of bacterial control. One such quorum sensing molecule is the sesquiterpene alcohol, Farnesol, which is synthesized and released by the fungus, Candida albicans. In most in-vivo cases, our laboratory has shown that Alcaligenes faecalis overtakes C. albicans, preventing its growth. However, as a way to counteract this inhibitory effect, Farnesol may be one way that Candida has found to fight back. In this study, we focused on ...


A Biogeographical Assessment Of Arctic Marine Fungi, Bentley E. Simpson May 2020

A Biogeographical Assessment Of Arctic Marine Fungi, Bentley E. Simpson

Honors College

Marine fungi play a crucial role in recycling nutrients and channeling energy to higher trophic levels in the world oceans. Despite their critical role, their distributions and community composition, particularly in the Arctic, are largely unknown. This study reveals depth-related trends of abundance, diversity, and community composition of Arctic marine fungi through analysis of data obtained in the Tara Oceans expedition. With samples from surface (0-50 m), deep chlorophyll max (50-200 m), and mesopelagic (200-1000 m) depths, relative abundance, operational taxonomic unit (OTU) richness, and diversity were found to increase as a function of depth. Basidiomycota and Ascomycota were found ...


The Coordinate Actions Of Calcineurin And Hog1 Mediate The Stress Response Through Multiple Nodes Of The Cell Cycle Network, Cassandra M. Leech, Mackenzie J. Flynn, Heather E. Arsenault, Jianhong Ou, Haibo Liu, Lihua Julie Zhu, Jennifer A. Benanti Apr 2020

The Coordinate Actions Of Calcineurin And Hog1 Mediate The Stress Response Through Multiple Nodes Of The Cell Cycle Network, Cassandra M. Leech, Mackenzie J. Flynn, Heather E. Arsenault, Jianhong Ou, Haibo Liu, Lihua Julie Zhu, Jennifer A. Benanti

Open Access Publications by UMMS Authors

Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the phosphatase calcineurin (CN) in the stress response and demonstrate that CN activates the Hog1/p38 pathway in both yeast and human cells. In yeast, the MAPK Hog1 is transiently activated in response to several well-studied osmostressors. We show that when a stressor simultaneously activates CN and Hog1, CN disrupts Hog1-stimulated negative feedback to prolong Hog1 ...


Dgts Production As A Phosphate Starvation Response In The Human Fungal Pathogen Candida Albicans, Caleb Wehling Apr 2020

Dgts Production As A Phosphate Starvation Response In The Human Fungal Pathogen Candida Albicans, Caleb Wehling

Dissertations and Theses in Biological Sciences

Betaine lipids are a class of membrane lipids with betaine head groups. Three betaine lipids are known - diacylglyceryltrimethylhomoserine (DGTS), diacylglycerylhydroxymethylalanine (DGTA), and diacylglycerylcarboxymethylcholine (DGCC). Betaine lipids are most common in algae, although DGTS, the most common betaine lipid, is also found in many bacteria and fungi. Organisms which produce betaine lipids (especially DGTS) often don’t produce phosphatidylcholine (PtdCho), and DGTS structure resembles PtdCho structure without any phosphorous, leading to the hypothesis that betaine lipids may substitute for phospholipids in some organisms. This has been confirmed by discoveries that some organisms are capable of switching their membrane composition from PtdCho ...


Comprehensive Fitness Maps Of Hsp90 Show Widespread Environmental Dependence, Julia M. Flynn, Ammeret Rossouw, Pamela A. Cote-Hammarlof, Ines Fragata, David Mavor, Carl Hollins Iii, Claudia Bank, Daniel N. Bolon Mar 2020

Comprehensive Fitness Maps Of Hsp90 Show Widespread Environmental Dependence, Julia M. Flynn, Ammeret Rossouw, Pamela A. Cote-Hammarlof, Ines Fragata, David Mavor, Carl Hollins Iii, Claudia Bank, Daniel N. Bolon

Open Access Publications by UMMS Authors

Gene-environment interactions have long been theorized to influence molecular evolution. However, the environmental dependence of most mutations remains unknown. Using deep mutational scanning, we engineered yeast with all 44,604 single codon changes encoding 14,160 amino acid variants in Hsp90 and quantified growth effects under standard conditions and under five stress conditions. To our knowledge, these are the largest determined comprehensive fitness maps of point mutants. The growth of many variants differed between conditions, indicating that environment can have a large impact on Hsp90 evolution. Multiple variants provided growth advantages under individual conditions; however, these variants tended to exhibit ...


Skp, Cullin, F-Box (Scf)-Met30 And Scf-Cdc4-Mediated Proteolysis Of Cenp-A Prevents Mislocalization Of Cenp-A For Chromosomal Stability In Budding Yeast, Wei-Chun Au, Richard E. Baker, Munira A. Basrai Feb 2020

Skp, Cullin, F-Box (Scf)-Met30 And Scf-Cdc4-Mediated Proteolysis Of Cenp-A Prevents Mislocalization Of Cenp-A For Chromosomal Stability In Budding Yeast, Wei-Chun Au, Richard E. Baker, Munira A. Basrai

Open Access Publications by UMMS Authors

Restricting the localization of the histone H3 variant CENP-A (Cse4 in yeast, CID in flies) to centromeres is essential for faithful chromosome segregation. Mislocalization of CENP-A leads to chromosomal instability (CIN) in yeast, fly and human cells. Overexpression and mislocalization of CENP-A has been observed in many cancers and this correlates with increased invasiveness and poor prognosis. Yet genes that regulate CENP-A levels and localization under physiological conditions have not been defined. In this study we used a genome-wide genetic screen to identify essential genes required for Cse4 homeostasis to prevent its mislocalization for chromosomal stability. We show that two ...


Novel Small Molecule Antifungals For Invasive Fungal Infections, Emily Dennis Jan 2020

Novel Small Molecule Antifungals For Invasive Fungal Infections, Emily Dennis

Theses and Dissertations--Pharmacy

Human fungal pathogens cause a range of diseases from benign skin conditions (i.e., ringworm) to thrush, mucosal membrane infections, and life-threatening systemic infections including bloodstream infections (i.e., aspergillosis and candidiasis) and Cryptococcal meningitis. These systemic infections occur most often in immunocompromised individuals and have high mortality rates. Current antifungal agents used in the clinic belong to three main classes: the polyenes (e.g., amphotericin B (AmB)), the echinocandins (e.g., caspofungin (CFG)), and the azoles (e.g., fluconazole (FLC)). In addition, the antimetabolite pyrimidine analogue flucytosine is used in combination with AmB. The three main classes class of ...


Investigating The Nucleophosmin (Npm1) Protein In The Context Of Protein Aggregation In The Budding Yeast S. Cerevisiae, Tyler Atagozli Jan 2020

Investigating The Nucleophosmin (Npm1) Protein In The Context Of Protein Aggregation In The Budding Yeast S. Cerevisiae, Tyler Atagozli

Honors Theses at the University of Iowa

The Nucleophosmin (Npm1) protein is a nucleolar protein found in jawed vertebrates. It is primarily involved in ribosome biogenesis. Recent studies have proposed a new role for this protein as a protective agent colocalizing with cellular aggregates like firefly luciferase and the mutant huntingtin protein during stress conditions. In this study, the behavior of Npm1 was investigated in the budding yeast S. cerevisiae by fluorescence microscopy to see if Npm1 colocalizes or otherwise interacts with aggregates. I found that Npm1 redistributes to a subnuclear location after heat shock where it may colocalize with luciferase aggregates. HTTQ103, a mutant huntingtin protein ...


Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer Jan 2020

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal ...


Evaluating Volatile Organic Compounds For Contact-Independent Antagonism Of Pseudogymnoascus Destructans Nov 2019

Evaluating Volatile Organic Compounds For Contact-Independent Antagonism Of Pseudogymnoascus Destructans

Symposium of Student Scholars

White-nose syndrome (WNS), a disease caused by the fungus Pseudogymnoascus destructans, is responsible for the extensive mortality of bats in the United States. In an effort to develop tools to reduce bat mortality attributed to WNS, an in vitro experiment was conducted to quantify the inhibitory effects of select volatile organic compounds (VOCs) as well as explore potential synergistic activities. The experiment involved exposing mycelial plugs of P. destructans to various concentrations of B23 as well as B23 and decanal together at equimolar ratios. Measurements of the plugs were taken over the course of the 13 day experiment allowing the ...


Oral Fungal Microbiota: To Thrush And Beyond, Dennis J. Baumgardner Oct 2019

Oral Fungal Microbiota: To Thrush And Beyond, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

The oral microbiota is complex, multikingdom, interactive, and involves extensive biofilm formation. While dominated by bacteria, Candida is a frequent member of this microbiota; however, several other potentially pathogenic fungi (among around 100 identified species) appear to reside in some individuals, including Cryptococcus, Aspergillus, and Fusarium. Oral candidiasis may manifest as a variety of disease entities in normal hosts and in the immunocompromised. These include pseudomembranous candidiasis (thrush), hyperplastic or atrophic (denture) candidiasis, linear gingival erythema, median rhomboid glossitis, and angular cheilitis. The purpose of this review is to describe the oral fungal microbiota (ie, oral mycobiota), common mouth diseases ...


Mdt-28/Plin-1 Mediates Lipid Droplet-Microtubule Interaction Via Dlc-1 In Caenorhabditis Elegans, Kang Xie, Peng Zhang, Huimin Na, Yangli Liu, Hong Zhang, Pingsheng Liu Oct 2019

Mdt-28/Plin-1 Mediates Lipid Droplet-Microtubule Interaction Via Dlc-1 In Caenorhabditis Elegans, Kang Xie, Peng Zhang, Huimin Na, Yangli Liu, Hong Zhang, Pingsheng Liu

Open Access Publications by UMMS Authors

Ectopic lipid accumulation in lipid droplets (LD) has been linked to many metabolic diseases. In this study, DHS-3::GFP was used as a LD marker in C. elegans and a forward genetic screen was carried out to find novel LD regulators. There were 140 mutant alleles identified which were divided into four phenotypic categories: enlarged, aggregated, aggregated and small, and decreased. After genetic mapping, mutations in three known LD regulatory genes (maoc-1, dhs-28, daf-22) and a peroxisome-related gene (acox-3) were found to enlarge LDs, demonstrating the reliability of using DHS-3 as a living marker. In the screen, the cytoskeleton protein ...


Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge Oct 2019

Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge

Open Access Publications by UMMS Authors

Cryptococcus gattii R265 is a hypervirulent fungal strain responsible for the recent outbreak of cryptococcosis in Vancouver Island of British Columbia in Canada. It differs significantly from Cryptococcus neoformans in its natural environment, its preferred site in the mammalian host, and its pathogenesis. Our previous studies of C. neoformans have shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the present investigation reveal that the ...


The Essential Role Of Carbon Metabolism In The Virulence Of Cryptococcus Neoformans, Mara Weigner Oct 2019

The Essential Role Of Carbon Metabolism In The Virulence Of Cryptococcus Neoformans, Mara Weigner

Senior Honors Theses

Cryptococcus neoformans infections are a major cause of meningoencephalitis in immunosuppressed patients worldwide. Inhaled as spores or desiccated yeast cells, C. neoformans can undergo metabolic changes in response to the new host environment that allow it to cross the blood brain barrier and cause deadly central nervous system (CNS) infections. Nutrient acquisition, and specifically carbon metabolism, is critical for survival and proliferation within the host. Notably, efficient carbon metabolism is necessary to produce the polysaccharide capsule, which is arguably C. neoformans’ most important and well-studied virulence factor. As such, a better understanding of carbon acquisition and regulation is essential for ...


Distinct Transcriptional Roles For Histone H3-K56 Acetylation During The Cell Cycle In Yeast, Salih Topal, Pauline Vasseur, Marta Radman-Livaja, Craig L. Peterson Sep 2019

Distinct Transcriptional Roles For Histone H3-K56 Acetylation During The Cell Cycle In Yeast, Salih Topal, Pauline Vasseur, Marta Radman-Livaja, Craig L. Peterson

Open Access Publications by UMMS Authors

Dynamic disruption and reassembly of promoter-proximal nucleosomes is a conserved hallmark of transcriptionally active chromatin. Histone H3-K56 acetylation (H3K56Ac) enhances these turnover events and promotes nucleosome assembly during S phase. Here we sequence nascent transcripts to investigate the impact of H3K56Ac on transcription throughout the yeast cell cycle. We find that H3K56Ac is a genome-wide activator of transcription. While H3K56Ac has a major impact on transcription initiation, it also appears to promote elongation and/or termination. In contrast, H3K56Ac represses promiscuous transcription that occurs immediately following replication fork passage, in this case by promoting efficient nucleosome assembly. We also detect ...


Coccidioidomycosis: Medical And Spatio-Temporal Perspectives, Nikias Sarafoglou, Rafael Laniado-Laborin, Menas Kafatos Sep 2019

Coccidioidomycosis: Medical And Spatio-Temporal Perspectives, Nikias Sarafoglou, Rafael Laniado-Laborin, Menas Kafatos

Mathematics, Physics, and Computer Science Faculty Articles and Research

Coccidioidomycosis (CM) is a disease of major public health importance due to the challenges in its diagnosis and treatment. To understand CM requires the attributes of a multidisciplinary network analysis to appreciate the complexity of the medical, the environmental and the social issues involved: public health, public policy, geology, atmospheric science, agronomy, social sciences and finally humanities, all which provide insight into this population transformation.

In section 1 of this paper, we describe the CM-epidemiology, the clinical features, the diagnosis and finally the treatment.

In section 2, we highlight the most important contributions and controversies in the history of the ...


Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii [Preprint], Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge Sep 2019

Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii [Preprint], Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge

University of Massachusetts Medical School Faculty Publications

Cryptococcus gattii R265 is a hyper-virulent fungal strain responsible for the major outbreak of cryptococcosis in Vancouver Island of British Columbia in 1999. It differs significantly from C. neoformans in its natural environment, its preferred site in the mammalian host, and in the nature and mode of pathogenesis. Our previous studies in C. neoformans have shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the ...


The Aminoalkylindole, Bml-190, Negatively Regulates Chitosan Synthesis Via The Camp/Pka1 Pathway In Cryptococcus Neoformans [Preprint], Brian T. Maybruck, Woei C. Lam, Charles A. Specht, Ma Xenia G. Ilagan, Maureen J. Donlin, Jennifer K. Lodge Aug 2019

The Aminoalkylindole, Bml-190, Negatively Regulates Chitosan Synthesis Via The Camp/Pka1 Pathway In Cryptococcus Neoformans [Preprint], Brian T. Maybruck, Woei C. Lam, Charles A. Specht, Ma Xenia G. Ilagan, Maureen J. Donlin, Jennifer K. Lodge

University of Massachusetts Medical School Faculty Publications

Cryptococcus neoformans can cause fatal meningoencephalitis in patients with AIDS or other immune-compromising conditions. Current antifungals are suboptimal to treat this disease, therefore, novel targets and new therapies are needed. Previously, we have shown that chitosan is a critical component of the cryptococcal cell wall, is required for survival in the mammalian host, and that chitosan deficiency results in rapid clearance from the mammalian host. We had also identified several specific proteins that were required for chitosan biosynthesis, and we hypothesize that screening for compounds that inhibit chitosan biosynthesis would identify additional genes/proteins that influence chitosan biosynthesis.