A5011309930- Antifungal resistance and susceptibility
- Bacterial biofilms and quorum sensing
- Allergic Rhinitis and Sensitization
- Fungal Infections and Studies
- Asthma and respiratory diseases
- Oral microbiology and periodontitis research
- Contact Dermatitis and Allergies
- Food Allergy and Anaphylaxis Research
- Probiotics and Fermented Foods
- Antimicrobial Peptides and Activities
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Resistance in Staphylococcus
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Insect and Pesticide Research
- Cholinesterase and Neurodegenerative Diseases
- Bacterial Infections and Vaccines
- Transgenic Plants and Applications
- Urinary Tract Infections Management
- Microbial Natural Products and Biosynthesis
- Fungal Plant Pathogen Control
- Biochemical and Structural Characterization
- Synthesis and Biological Evaluation
- Fungal and yeast genetics research
- Indoor Air Quality and Microbial Exposure
University of Wisconsin–Madison
2015-2024
Highland Community College - Illinois
2021
William S. Middleton Memorial Veterans Hospital
1997-2009
Dupont Hospital
2005
Memorial Hospital of South Bend
2004
Peking Union Medical College Hospital
2003
Chinese Academy of Medical Sciences & Peking Union Medical College
2003
Beijing Radiation Center
2003
Madison Group (United States)
1999
United States Department of Veterans Affairs
1997
Virulence of Candida is linked with its ability to form biofilms. Once established, biofilm infections are nearly impossible eradicate. Biofilm cells live immersed in a self-produced matrix, blend extracellular biopolymers, many which uncharacterized. In this study, we provide comprehensive analysis the matrix manufactured by albicans both vitro and clinical niche animal model. We further explore function components, including impact on drug resistance. uncovered components from each...
Extracellular polysaccharides are key constituents of the biofilm matrix many microorganisms. One critical carbohydrate component Candida albicans biofilms, β-1,3 glucan, has been linked to protection from antifungal agents. In this study, we identify three glucan modification enzymes that function deliver cell extracellular matrix. These include two predicted transferases and an exo-glucanase, encoded by BGL2, PHR1, XOG1, respectively. We show crucial for both delivery accumulation mature...
Cells from all kingdoms of life produce extracellular vesicles (EVs). Their cargo is protected the environment by surrounding lipid bilayer. EVs many organisms have been shown to function in cell–cell communication, relaying signals that impact metazoan development, microbial quorum sensing, and pathogenic host–microbe interactions. Here, we investigated production functional activities a surface-associated community or biofilm fungal pathogen Candida albicans. Crowded communities like...
New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Candida auris. Leveraging microbiomes marine animals cutting-edge metabolomics genomic tools, we identified encouraging lead molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent vitro mouse-model efficacy toward multiple-drug-resistant pathogens, exhibits a wide safety index, functions through fungal-specific...
Medical devices provide an ecological niche for microbes to flourish as a biofilm community, protected from antimicrobials and host defenses. Biofilms formed by Candida albicans, the most common fungal pathogen, survive exposure extraordinarily high drug concentrations. Here, we show that beta-glucan synthase Fks1p produces glucan, which is deposited in matrix. The extracellular glucan required resistance acts sequestering antifungals, rendering cells resistant their action. These findings...
ABSTRACT Candida albicans frequently infects medical devices by growing as a biofilm, i.e., community of adherent organisms entrenched in an extracellular matrix. During biofilm growth, spp. acquire the ability to resist high concentrations antifungal drugs. One recently recognized resistance mechanism involves drug sequestration matrix β-1,3 glucan. Using candidate gene approach, we investigated potential C. β-1,3-glucan regulators, based on their homology Saccharomyces cerevisiae ,...
Significance Candida albicans is the most common fungal pathogen and frequently grows as a biofilm. These adherent communities tolerate extremely high concentrations of antifungals due in large part to protective extracellular matrix. The present studies observe novel reliance on multiple matrix constituents for structure function. Furthermore, results demonstrate how biofilm community assembles these components space. Our findings reveal coordinated mechanism by which defining trait...
Fungal-bacterial interactions generate unique biofilms that cause many infections in humans. Candida albicans interact with Streptococcus mutans dental associated severe childhood tooth-decay, a prevalent pediatric oral disease. Current modalities are ineffective and primarily based on antimicrobial monotherapies despite the polymicrobial nature of infection. Here, we show combination clinically used topical antifungal fluconazole povidone iodine (PI) can completely suppress C. carriage...
Candida auris has emerged as an outbreak pathogen associated with high mortality. Biofilm formation and linked drug resistance are common among species. Drug sequestration by the biofilm matrix accounts for much of antifungal tolerance. In this study, we examine composition function a diverse set C. isolates. We show that sequesters nearly 70% available triazole antifungal. Like biofilms formed other spp., find is rich in mannan-glucan polysaccharides demonstrate their hydrolysis reduces...
Abstract The fungus Candida albicans is an opportunistic pathogen that can exploit imbalances in microbiome composition to invade its human host, causing pathologies ranging from vaginal candidiasis fungal sepsis. Bacteria of the genus Lactobacillus are colonizers mucosa and produce compounds with bioactivity against C. . Here, we show some species a small molecule under laboratory conditions blocks yeast-to-filament transition, important virulence trait. It remains unexplored whether...
Abstract The fungal pathogen Candida albicans can form biofilms that protect it from drugs and the immune system. biofilm cells release extracellular vesicles (EVs) promote matrix formation resistance to antifungal drugs. Here, we define functions for numerous EV cargo proteins in assembly drug resistance, as well cell adhesion dissemination. We use a machine-learning analysis of proteomic data mutants with production defects identify 63 candidate gene products which construct mutant...
Candida biofilm infections pose an increasing threat in the health care setting due to drug resistance associated with this lifestyle. Several mechanisms underlie phenomenon. In albicans, one mechanism involves impedance by matrix linked β-1,3 glucan. Here, we show is important for other spp. We identified glucan matrix, found that sequesters antifungal drug, and enhanced susceptibility hydrolysis.
Candida albicans is a fungal species that part of the normal human microbiota and also an opportunistic pathogen capable causing mucosal systemic infections. C. cells proliferate in planktonic (suspension) state, but they form biofilms, organized tightly packed communities attached to solid surface. Biofilms colonize many niches body persist on implanted medical devices, where are major source new Here, we used unbiased global substrate-profiling approach discover proteolytic activities...
biofilms resist the effects of available antifungal therapies. Prior studies with
Abstract Fungal infections cause more than 1.5 million deaths annually. With an increase in immune-deficient susceptible populations and the emergence of antifungal drug resistance, there is urgent need for novel strategies to combat these life-threatening infections. Here, we use a combinatorial screening approach identify imidazopyrazoindole, NPD827, that synergizes with fluconazole against azole-sensitive -resistant isolates Candida albicans . NPD827 interacts sterols, resulting profound...
Extracellular vesicles mediate community interactions among cells ranging from unicellular microbes to complex vertebrates. of the fungal pathogen Candida albicans are vital for biofilm communities produce matrix, which confers environmental protection and modulates dispersion. Infections increasingly due diverse species, such as emerging auris, well mixed communities. Here, we define composition function biofilm-associated five species across genus. We find similarities in vesicle size...
Until recently, NADPH oxidase (NOX) enzymes were thought to be a property of multicellularity, where the reactive oxygen species (ROS) produced by NOX acts in signaling processes or attacking invading microbes through oxidative damage. We demonstrate here that unicellular yeast and opportunistic fungal pathogen Candida albicans is capable ROS burst using member enzyme family, which we identify as Fre8. C. can exist either yeast-like budding form filamentous multicellular hyphae pseudohyphae,...
ABSTRACT Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to device surface and propagate as a biofilm. These biofilm communities differ from free-floating , exhibiting high tolerance antifungal therapy. The significance catheter-associated candiduria is often unclear, treatment may be problematic considering drug-resistant phenotype. Here we describe rodent model for study albicans infection that mimics this common process In...
The emergence of drug-resistant fungi has prompted an urgent threat alert from the US Centers for Disease Control (CDC). Biofilm assembly by these pathogens further impairs effective therapy. We recently identified antifungal, turbinmicin, that inhibits fungal vesicle-mediated trafficking pathway and demonstrates broad-spectrum activity against planktonically growing fungi. During biofilm growth, vesicles with unique features play a critical role in delivery extracellular matrix components....
Rising drug resistance among pathogenic fungi, paired with a limited antifungal arsenal, poses an increasing threat to human health. To identify compounds, we screened the RIKEN natural product depository against representative isolates of four major fungal pathogens. This screen identified NPD6433, triazenyl indole broad-spectrum activity all screening strains, as well filamentous mold Aspergillus fumigatus. Mechanistic studies indicated that NPD6433 targets enoyl reductase domain fatty...
APX001, the prodrug of APX001A, is a first-in-class antifungal agent that has potent activity against Aspergillus fumigatus The goal current study was to determine pharmacodynamic (PD) index and target APX001 in an immunocompromised murine model invasive pulmonary aspergillosis 6 A. isolates. Minimum effective concentration (MEC) values ranged from 0.03 0.06 mg/liter. Dose fractionation performed isolate AF293 using total doses ranging 81 768 mg/kg body weight/day fractionated into every 3-,...
Biofilm formation on implanted medical devices is a major source of lethal invasive infection by Candida albicans. Filamentous growth this fungus tied to biofilm because many filamentation-associated genes are required for surface adherence. Cell cycle or cell defects can induce filamentation, but we have limited information about the coupling between filamentation and gene expression after cycle/cell inhibition. Here identified CDK activating protein kinase Cak1 as determinant through...
Abstract Fungal pathogens are a continuing challenge due to few effective antifungals and rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis . Here, optimize EntV as potential therapeutic better understand its antifungal features, an X-ray structure is obtained. The consists six alpha helices enclosing seventh 16 helix (α7). individual tested for activity using...
Implanted medical devices such as central venous catheters are highly susceptible to microbial colonization and biofilm formation a major risk factor for nosocomial infections. The opportunistic pathogen Pseudomonas aeruginosa uses exopolysaccharides, Psl, both initial surface attachment formation. We have previously shown that chemically immobilizing the Psl-specific glycoside hydrolase, PslGh, material can inhibit P. Herein, we show PslGh be uniformly immobilized on lumen of medical-grade,...