A5107387269- Genetics, Aging, and Longevity in Model Organisms
- Antimicrobial Peptides and Activities
- Antimicrobial Resistance in Staphylococcus
- Porphyrin Metabolism and Disorders
- Biochemical Acid Research Studies
- Biochemical and Structural Characterization
- Mitochondrial Function and Pathology
- Photosynthetic Processes and Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Bacterial biofilms and quorum sensing
- Synthesis and biological activity
- Antifungal resistance and susceptibility
- Genomics, phytochemicals, and oxidative stress
- Microbial Fuel Cells and Bioremediation
- Insect Resistance and Genetics
- Antibiotics Pharmacokinetics and Efficacy
- Pharmacological Effects of Natural Compounds
- RNA Interference and Gene Delivery
- Botulinum Toxin and Related Neurological Disorders
- Eosinophilic Esophagitis
- Biochemical Analysis and Sensing Techniques
- Insect Utilization and Effects
- Vibrio bacteria research studies
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Phenothiazines and Benzothiazines Synthesis and Activities
Rhode Island Hospital
2014-2022
Brown University
2014-2022
Massachusetts General Hospital
2014-2022
Harvard University
2014-2020
Office of Infectious Diseases
2014
Providence College
2014
Loewe Center for Synthetic Microbiology
2013
Max Planck Institute for Terrestrial Microbiology
2013
Philipps University of Marburg
2005-2012
Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks costs compared to de novo development novel agents. In this study, we examined properties two commercially available anthelmintic drugs. The FDA drug niclosamide veterinary oxyclozanide displayed strong vivo vitro activity against methicillin resistant S....
Staphylococcus aureus, the leading cause of hospital-acquired infections in United States, is also pathogenic to model nematode Caenorhabditis elegans. The C. elegans-S. aureus infection was previously carried out on solid agar plates where bacteriovorous elegans feeds a lawn S. aureus. However, agar-based assays are not amenable large scale screens for antibacterial compounds. We have developed high throughput liquid screening assay that uses robotic instrumentation dispense precise amount...
The rise of multidrug-resistant Acinetobacter baumannii and a concomitant decrease in antibiotic treatment options warrants search for new classes antibacterial agents. We have found that A. is pathogenic lethal to the model host organism Caenorhabditis elegans exploited this phenomenon develop an automated, high-throughput, high-content screening assay liquid culture can be used identify novel antibiotics effective against baumannii. involves coincubating C. with 384-well plates containing...
The increasing prevalence of antibiotic resistance has created an urgent need for alternative drugs with new mechanisms action. Antimicrobial peptides (AMPs) are promising candidates that could address the spread multidrug-resistant bacteria, either alone or in combination conventional antibiotics. We studied antimicrobial efficacy and bactericidal mechanism cecropin A2, a 36-residue α-helical cationic peptide derived from Aedes aegypti A, focusing on common pathogen Pseudomonas aeruginosa...
ABSTRACT The anaerobic acetogenic bacterium Acetobacterium woodii couples caffeate reduction with electrons derived from hydrogen to the synthesis of ATP by a chemiosmotic mechanism sodium ions as coupling ions, process referred respiration. We addressed nature hitherto unknown enzymatic activities involved in this and their cellular localization. Cell extract A. catalyzes H 2 -dependent reduction. This reaction is strictly dependent but can be activated also acetyl coenzyme A (CoA),...
Background: NH125, a known WalK inhibitor kills MRSA persisters. However, its precise mode of action is still unknown. Methods & results: The NH125 was investigated by comparing spectrum antimicrobial activity and effects on membrane permeability giant unilamellar vesicles (GUVs) with walrycin B, WalR benzyldimethylhexadecylammonium chloride (16-BAC), cationic surfactant. killed persister cells variety Staphylococcus aureus strains. Similar to 16-BAC, persisters inducing rapid...
Significance Eukaryotes and bacteria are often in dialogue, some cases mutualistic other pathogenic. A highly evolved system of measures countermeasures by both eukaryotic host may mediate these interactions. Here we found that mutations the electron transport pathway normally benign Escherichia coli , which is a food for Caenorhabditis elegans laboratory, induces mitochondrial stress response. The oxidatively stressed E. activates responses via transcription factors known to homeostasis....
Conventional antibiotics are not effective in treating infections caused by drug-resistant or persistent nongrowing bacteria, creating a dire need for the development of new antibiotics. We report that small molecule nTZDpa, previously characterized as nonthiazolidinedione peroxisome proliferator-activated receptor gamma partial agonist, kills both growing and Staphylococcus aureus cells lipid bilayer disruption. S. exhibited no detectable resistance to compound acted synergistically with...
Candida albicans is a ubiquitous fungus, which can cause very serious and sometimes life-threatening infections in susceptible patients. We used Caenorhabditis elegans as model host to screen library of C. mutants for decreased virulence identified SPT20 important virulence. The transcription co-activator was originally suppressor Ty solo δ insertion mutations, defects Saccharomyces cerevisiae. It resistant the toxicity caused by overexpression GAL4-VP16. constructed spt20Δ/Δ mutant found...
The red flour beetle Tribolium castaneum is a common insect pest and has been established as model to study development immunity. This demonstrates that defensin 1 from T. displays in vitro vivo antimicrobial activity against drug resistant Staphylococcus aureus strains. minimum inhibitory concentration (MIC) of 11 reference clinical staphylococcal isolates was between 16–64 μg/ml. putative mode action the peptide disruption bacterial cell membrane. antibacterial attenuated by salt...
Caenorhabditis elegans is a valuable tool as an infection model toward the study of Candida species. In this work, we endeavored to develop C. elegans-Candida parapsilosis by using fungi food source. Three species complex (C. (sensu stricto), orthopsilosis and metapsilosis) caused resulting in killing. All three strains that comprised significantly diminished nematode lifespan, indicating virulence pathogens against host. The process included invasion intestine vulva which resulted organ...
Aim: Compound 1-(4-chlorophenyl)-4,4,4-trifluoro-3-hydroxy-2-buten-1-one (compound 1) was identified as a hit against methicillin-resistant Staphylococcus aureus (MRSA) strain MW2. Methods & results: The MIC of compound 1 MRSA 4 μg/ml. showed enhanced activity at acidic pH by lowering bacterial intracellular and exhibited no lysis human red blood cells up to 64 μg/ml its IC50 HepG2 32 reduced 1-log10 colony forming units in macrophages prolonged the survival MRSA-infected Caenorhabditis...
Francisella tularensis is a highly infectious Gram-negative intracellular pathogen that causes tularemia. Because of its potential as bioterrorism agent, there need for new therapeutic agents. We therefore developed whole-animal Caenorhabditis elegans-F. pathosystem high-throughput screening to identify and characterize compounds. found the C. elegans p38 mitogen-activate protein (MAP) kinase cascade involved in immune response F. tularensis, we robust tularensis-mediated killing assay with...
Significance The animal mitochondrion has a bacterial origin and depends on vitamins other biochemicals produced by bacteria. In genetic search for mitochondrial biochemical dependencies when the Caenorhabditis elegans is feeding Escherichia coli as its sole nutritional source, we identified 45 E. mutations that disrupt function. Four of these transport removal iron from an retrieval cofactor were lethal in combination with C. mutations. Antioxidants strongly suppressed this inviability,...
Abstract Microbial toxins and virulence factors often target the eukaryotic translation machinery. Caenorhabditis elegans surveils for such microbial attacks by monitoring translational competence, if a deficit is detected, particular drug detoxification bacterial defense genes are induced. The bacteria Kocuria rhizophila has evolved countermeasures to animal surveillance pathways. Here, we used comprehensive genetic analysis of identify pathways that inhibit C. toxin defense. mutations...