A5000754889- Genetics, Aging, and Longevity in Model Organisms
- Bacterial biofilms and quorum sensing
- Gut microbiota and health
- Vibrio bacteria research studies
- Antimicrobial Resistance in Staphylococcus
- Antibiotic Resistance in Bacteria
- Bacterial Infections and Vaccines
- Circadian rhythm and melatonin
- Bacterial Genetics and Biotechnology
- Biochemical and Molecular Research
- Influenza Virus Research Studies
- Nanoparticles: synthesis and applications
- CRISPR and Genetic Engineering
- Immune Response and Inflammation
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Tryptophan and brain disorders
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Escherichia coli research studies
- Parasites and Host Interactions
- Legionella and Acanthamoeba research
- Diet and metabolism studies
New York Academy of Sciences
2023
John Wiley & Sons (Germany)
2023
Moss Landing Marine Laboratories
2023
Hudson Institute
2023
Roche (United States)
2023
Stanford University
2002-2014
Genentech
2013
Office of Infectious Diseases
2013
Bipar
2010-2011
Brandeis University
2011
We show that a single clinical isolate of the human opportunistic pathogen Pseudomonas aeruginosa (strain PA14), which previously was shown to be pathogenic in mice and plants, also kills Caenorhabditis elegans. The rate PA14-mediated killing C. elegans depends on composition agar medium PA14 is grown. When grown minimal medium, occurs over course several days referred as "slow" killing. high-osmolarity hours "fast" Several lines evidence, including fact heat-killed bacteria are still...
A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa led the identification of two genes required pathogen resistance: sek-1 , which encodes a mitogen-activated protein (MAP) kinase kinase, and nsy-1 MAP kinase. RNA interference assays biochemical analysis established that p38 ortholog, pmk-1 functions as downstream defense. These data suggest this signaling cassette represents an ancient feature innate immune responses in...
We reported recently that the human opportunistic pathogen Pseudomonas aeruginosa strain PA14 kills Caenorhabditis elegans and many P. virulence factors (genes) required for maximum in mouse pathogenicity are also killing of C. elegans. Here we report among eight Tn phoA mutants isolated exhibited reduced , at least five mice. Three corresponded to known virulence-related genes lasR, gacA lemA . ( aefA from Escherichia coli, pstP Azotobacter vinelandii mtrR Neisseria gonorrhoeae ) had not...
The strong restriction barrier present in Staphylococcus aureus and epidermidis has limited functional genomic analysis to a small subset of strains that are amenable genetic manipulation. Recently, conserved type IV system termed SauUSI (which specifically recognizes cytosine methylated DNA) was identified as the major transformation with foreign DNA. Here we have independently corroborated these findings widely used laboratory strain S. aureus. Additionally, constructed DNA...
We used plants as an in vivo pathogenesis model for the identification of virulence factors human opportunistic pathogen Pseudomonas aeruginosa . Nine nine Tn phoA mutant derivatives P. strain UCBPP-PA14 that were identified a plant leaf assay less pathogenic mutants also exhibited significantly reduced pathogenicity burned mouse model, suggesting utilizes common strategies to infect both hosts. Seven these contain insertions previously unknown genes. These results demonstrate alternative...
Innate immunity is an ancient and conserved defense mechanism. Although host responses toward various pathogens have been delineated, how these are orchestrated in a whole animal less understood. Through unbiased genome-wide study performed Caenorhabditis elegans, we identified function for endodermal GATA transcription factors regulating local epithelial innate immune responses. Gene expression functional RNAi-based analyses the tissue-specific factor ELT-2 as major regulator of early...
Some pathogens have evolved mechanisms to overcome host immune defenses by inhibiting defense signaling pathways and suppressing the expression of effectors. We present evidence that Pseudomonas aeruginosa is able suppress a subset genes in animal Caenorhabditis elegans activating DAF-2/DAF-16 insulin-like pathway. The pathway important for regulation many aspects organismal physiology, including metabolism, stress response, longevity, function. show intestinal DAF-16 required resistance P....
Abstract The ability to avoid noxious extremes of hot and cold is critical for survival depends on thermal nociception. TRPV subset transient receptor potential (TRP) channels heat activated proposed be responsible detection in vertebrates fruit flies. To gain insight into the genetic neural basis nociception, we developed assays that quantify avoidance nematode Caenorhabditis elegans used them investigate this behavior. First, screened mutants 18 TRP channel genes (including all orthologs)...
Abstract Acinetobacter baumannii is a highly antibiotic resistant Gram-negative bacterium that causes life-threatening infections in humans with very high mortality rate. A. an extracellular pathogen poorly understood virulence mechanisms. Here we report employs the release of outer membrane vesicles (OMVs) containing protein A (OmpA Ab ) to promote bacterial pathogenesis and dissemination. OMVs OmpA are taken up by mammalian cells where they activate host GTPase dynamin-related 1 (DRP1)....
IL-22 is induced by aryl hydrocarbon receptor (AhR) signaling and plays a critical role in gastrointestinal barrier function through effects on antimicrobial protein production, mucus secretion, epithelial cell differentiation proliferation, giving it the potential to modulate microbiome these direct indirect effects. Furthermore, can turn influence production synthesis of L-tryptophan (L-Trp)-derived AhR ligands, creating prospect host-microbiome feedback loop. We evaluated impact may have...
Summary The Caenorhabditis elegans DAF‐2 insulin‐like signaling pathway, which regulates lifespan and stress resistance, has also been implicated in resistance to bacterial pathogens. Loss‐of‐function daf‐2 age‐1 mutants have increased lifespans are resistant a variety of This raises the possibility that longevity pathogen pathway reflections same underlying mechanism. Here we report regulation Pseudomonas aeruginosa is mediated by both shared genetically distinguishable mechanisms. We find...
Broadly neutralizing antibodies targeting the stalk region of influenza A virus (IAV) hemagglutinin (HA) are effective in blocking infection both vitro and vivo. The highly conserved epitopes recognized by these critical for membrane fusion function HA therefore less likely to be permissive mutational escape. Here we report three resistant viruses A/Perth/16/2009 strain that were selected presence a broadly stalk-binding antibody. harbor different mutations stalk: (1) Gln387Lys; (2)...
Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an unusual family staphylococcal adhesive proteins that contain long stretches serine-aspartate dipeptide-repeats (SDR). The prototype member this is clumping factor A (ClfA), a key virulence mediates adhesion to binding extracellular matrix such as fibrinogen. However, the biological siginificance SDR-domain its implication for pathogenesis remain poorly understood. Here, we identified two novel bacterial...
Little is known about the expression of methicillin-resistant Staphylococcus aureus (MRSA) genes during infection conditions. Here, we described transcriptome clinical MRSA strain USA300 derived from human cutaneous abscesses, and compared it with bacteria infected kidneys in a mouse model. Remarkable similarity between transcriptomes allowed us to identify encoding multiple proteases toxins, iron- peptide-transporter molecules, which are upregulated both infections likely important for...
Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested vitro and protects mice against lethal challenge of when administered 72 h post infection. demonstrates superior therapeutic benefit over Tamiflu has additive antiviral effect combination with Tamiflu. binds conserved epitope vestigial esterase domain hemagglutinin (HA) blocks...