A5043659327- Bacillus and Francisella bacterial research
- Bacterial Genetics and Biotechnology
- Insect symbiosis and bacterial influences
- Viral Infections and Outbreaks Research
- Antifungal resistance and susceptibility
- Bacteriophages and microbial interactions
- Fungal and yeast genetics research
- Invertebrate Immune Response Mechanisms
- Mosquito-borne diseases and control
- Polyamine Metabolism and Applications
- Antimicrobial Peptides and Activities
- Antibiotic Resistance in Bacteria
- Insect-Plant Interactions and Control
- Insect and Pesticide Research
- Escherichia coli research studies
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Viral Infections and Vectors
- Fungal Infections and Studies
- Toxin Mechanisms and Immunotoxins
- Plant Parasitism and Resistance
- Phenothiazines and Benzothiazines Synthesis and Activities
- Fungal Biology and Applications
- Insect Resistance and Genetics
Keck Graduate Institute
2015-2021
Stanford University
2008-2010
Biotechnology Research Institute
2007
National Academies of Sciences, Engineering, and Medicine
2006
National Research Council Canada
2005
Concordia University
2003
Recent sequencing and assembly of the genome for fungal pathogen Candida albicans used simple automated procedures identification putative genes. We have reviewed entire assembly, both by hand with additional bioinformatic resources, to accurately map describe 6,354 genes identify 246 whose original database entries contained errors (or possibly mutations) that affect their reading frame. Comparison other genomes permitted numerous fungus-specific might be targeted antifungal therapy. also...
12-Hydroxyjasmonate, also known as tuberonic acid, was first isolated from Solanum tuberosum and shown to have tuber-inducing properties. It is derived the ubiquitously occurring jasmonic an important signaling molecule mediating diverse developmental processes plant defense responses. We report here that gene AtST2a Arabidopsis thaliana encodes a hydroxyjasmonate sulfotransferase. The recombinant protein found exhibit strict specificity for 11- 12-hydroxyjasmonate with Km values of 50 10...
Abstract A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance antimicrobial countermeasures. Potentially, targeting host proteins pathways essential for detrimental effects pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures circumvent pathogen mutations leading resistance. Here we report implementation a strategy discovering host-oriented therapies against multiple pathogenic agents by multiplex...
Diverse pathogenic agents often utilize overlapping host networks, and hub proteins within these networks represent attractive targets for broad-spectrum drugs. Using bacterial toxins, we describe a new approach discovering therapies capable of inhibiting that mediate multiple pathways. This can be widely used, as it combines genetic-based target identification with cell survival-based protein function-based multiplex drug screens, concurrently discovers therapeutic compounds their targets....
We used Drosophila melanogaster macrophage-like Schneider 2 (S2) cells as a model to study cell-mediated innate immunity against infection by the opportunistic fungal pathogen Candida albicans. Transcriptional profiling of S2 coincubated with C. albicans revealed up-regulation several genes. One most highly up-regulated genes during this interaction is D. translational regulator 4E-BP encoded Thor gene. Analysis 4E-BP(null) mutant survival upon showed that plays an important role in host...
Many putative transcription factors in the pathogenic fungus Candida albicans contain sequence similarity to well-defined transcriptional regulators budding yeast Saccharomyces cerevisiae, but this is often limited DNA binding domains of molecules. The Gcn4p and Gal4p proteins cerevisiae are highly studied well-understood eukaryotic basic leucine zipper (Gcn4p) C(6) zinc cluster (Gal4p) families; C. has (CaGcn4p) CaGal4p with similar their S. counterparts. Deletion analysis CaGcn4p protein...
Anthrax is a major zoonotic disease of wildlife, and in places like West Africa, it can be caused by Bacillus anthracis arid nonsylvatic savannahs, B. cereus biovar (Bcbva) sylvatic rainforests. Bcbva-caused anthrax has been implicated as much 38% mortality rainforest ecosystems, where insects enhance the transmission anthrax-causing bacteria. While well-characterized mammals, its points to an unidentified anthrax-resistance mechanism vectors. In secreted toxin component, 83 kDa Protective...
Inflammasomes activate caspase-1 in response to molecular signals from pathogens and other dangerous stimuli as a part of the innate immune response. A previous study discovered small-molecule, 4-fluoro- N'-[1-(2-pyridinyl)ethylidene]benzohydrazide, which we named DN1, that reduces cytotoxicity anthrax lethal toxin (LT). We determined DN1 protected cells irrespectively LT concentration reduced pathogenicity an additional bacterial exotoxin several viruses. Using pathway, show does not...
Of the numerous infectious diseases afflicting humans, anthrax disease, caused by Bacillus anthracis, poses a major threat in its virulence and lack of effective treatment. The currently lacking standards care, as well lengthy drug approval process, demonstrate pressing demand for treatment B. anthracis infections. present study screened 1586 clinically approved drugs an attempt to identify repurposable compounds against cereus, relative strain that shares many physical genetic...
Abstract The major limitations of pathogen-directed therapies are the emergence drug-resistance and their narrow spectrum coverage. A recently applied approach directs against host proteins exploited by pathogens in order to circumvent these limitations. However, host-oriented drugs leave unaffected may result continued pathogen dissemination. In this study we aimed discover that could simultaneously cross-inhibit pathogenic agents, as well mediate lethality. We observed many host-assisting...
The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library 1586 FDA-approved drugs was screened against A. calcoaceticus, representative Acinetobacter calcoaceticus-baumannii complex. Three compounds were found to have previously undiscovered properties calcoaceticus: antifungal Miconazole, anthelminthic Dichlorophen, and Bithionol. These three tested wide range Gram-positive Gram-negative bacteria...
The genders of Drosophila melanogaster vary in their sensitivities to microbial pathogens. While many the immunity-related genes are located on X chromosome, polymorphisms within Y chromosome were also shown affect immunity flies. In this study, we investigated necessity individual (Y-genes) for male sensitivity microbes. We identified several Y-genes whose genetic inactivation either increases or decreases males gastrointestinal infections with fungal Saccharomyces cerevisiae and bacterial...
Anthrax is caused by Bacillus anthracis and can result in nearly 100% mortality due part to anthrax toxin. Antimalarial amodiaquine (AQ) acts as a host-oriented inhibitor of toxin endocytosis. Here, we determined the pharmacokinetics safety AQ mice, rabbits, humans well efficacy fly, mouse, rabbit models infection. In therapeutic-intervention studies, doubled survival mice infected subcutaneously with B. dose lethal 60% animals (LD60). rabbits challenged 200 LD50 aerosolized anthracis,...
Tryptophan, phenylalanine, tyrosine, and several other metabolites are all synthesized from a common precursor, chorismic acid. Since tryptophan is product of an energetically expensive biosynthetic pathway, bacteria have developed sensing mechanisms to downregulate synthesis the enzymes formation when amino acid not needed. In Bacillus subtilis some Gram-positive bacteria, trp operon expression regulated by two proteins, TRAP (the tryptophan-activated RNA binding protein) AT anti-TRAP...