A5067852918- Streptococcal Infections and Treatments
- Antimicrobial Resistance in Staphylococcus
- Neonatal and Maternal Infections
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pneumonia and Respiratory Infections
- Antimicrobial Peptides and Activities
- Bacterial Identification and Susceptibility Testing
- Bacterial biofilms and quorum sensing
- Antibiotic Resistance in Bacteria
- Infective Endocarditis Diagnosis and Management
- Inflammasome and immune disorders
- Bacterial Infections and Vaccines
- Glycosylation and Glycoproteins Research
- Microbial Natural Products and Biosynthesis
- Sepsis Diagnosis and Treatment
- Biochemical and Structural Characterization
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Antibiotics Pharmacokinetics and Efficacy
- Bacterial Genetics and Biotechnology
- Monoclonal and Polyclonal Antibodies Research
- Clostridium difficile and Clostridium perfringens research
University of California, San Diego
2016-2025
University of Montana
2016-2025
Rady Children's Hospital-San Diego
2010-2022
Osaka University
2022
Children's Hospital of Orange County
2021
Hallym University Sacred Heart Hospital
2021
Universidad Católica Santo Domingo
2014-2020
La Jolla Alcohol Research
2012-2020
University of Rhode Island
2019
Rhode Island College
2019
ABSTRACT Widespread antibiotic use in clinical medicine and the livestock industry has contributed to global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii . We report on a method used produce personalized bacteriophage-based therapeutic treatment for 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. infection. Despite multiple courses efforts at percutaneous drainage pancreatic pseudocyst, deteriorated over...
Cells must amplify external signals to orient and migrate in chemotactic gradient fields. We find that human neutrophils release adenosine triphosphate (ATP) from the leading edge of cell surface direct orientation by feedback through P2Y2 nucleotide receptors. Neutrophils rapidly hydrolyze released ATP then acts via A3-type receptors, which are recruited edge, promote migration. Thus, autocrine A3 receptors provide signal amplification, controlling sensing migration neutrophils.
Golden color imparted by carotenoid pigments is the eponymous feature of human pathogen Staphylococcus aureus. Here we demonstrate a role this hallmark phenotype in virulence. Compared with wild-type (WT) bacterium, S. aureus mutant disrupted biosynthesis more susceptible to oxidant killing, has impaired neutrophil survival, and less pathogenic mouse subcutaneous abscess model. The survival advantage WT over carotenoid-deficient lost upon inhibition oxidative burst or murine nicotinamide...
Hypoxia is a characteristic feature of the tissue microenvironment during bacterial infection. Here we report on our use conditional gene targeting to examine contribution hypoxia-inducible factor 1, α subunit (HIF-1α) myeloid cell innate immune function. HIF-1α was induced by infection, even under normoxia, and regulated production key effector molecules, including granule proteases, antimicrobial peptides, nitric oxide, TNF-α. Mice lacking in their lineage showed decreased bactericidal...
Iron is essential for many biological processes, including oxygen delivery, and its supply tightly regulated. Hepcidin, a small peptide synthesized in the liver, key regulator of iron absorption homeostasis mammals. Hepcidin production increased by overload decreased anemia hypoxia; but molecular mechanisms that govern hepcidin response to these stimuli are not known. Here we establish von Hippel–Lindau/hypoxia-inducible transcription factor (VHL/HIF) pathway an link between regulation vivo....
Significance Clinical evidence has indicated that the systemic spread of endotoxins from septic infection plays a crucial role in pathogenesis Gram-negative bacterial sepsis. However, currently there are no effective ways to manage diverse released by different genus, species, and strain. Herein, we demonstrate therapeutic potential macrophage-like nanoparticle for sepsis control through powerful two-step neutralization process: endotoxin first step followed cytokine sequestration second...
Staphylococcus aureus produces hospital- and community-acquired infections, with methicillin-resistant S. posing a serious public health threat. The golden carotenoid pigment of aureus, staphyloxanthin, promotes resistance to reactive oxygen species host neutrophil-based killing, early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. We determined the crystal structures dehydrosqualene synthase (CrtM) at 1.58 angstrom resolution, finding structural...
Neutrophils are key effectors of the host innate immune response against bacterial infection. <i>Staphylococcus aureus</i> is a preeminent human pathogen, with an ability to produce systemic infections even in previously healthy individuals, thereby reflecting resistance effective neutrophil clearance. The recent discovery extracellular traps (NETs) has opened novel dimension our understanding how these specialized leukocytes kill pathogens. NETs consist nuclear DNA backbone...
Abstract Sepsis, the leading cause of death in intensive care units, reflects a detrimental host response to infection which bacteria or LPS act as potent activators immune cells, including monocytes and macrophages. In this report, we show that raises level transcriptional regulator hypoxia-inducible factor-1α (HIF-1α) macrophages, increasing HIF-1α decreasing prolyl hydroxylase mRNA production TLR4-dependent fashion. Using murine conditional gene targeting myeloid lineage, demonstrate is...
Significance Microbes have the genetic capacity to produce large numbers of specialized compounds, yet only a small fraction these in laboratory. Here we introduce platform that allows efficient production natural product molecules from uncharacterized gene collections. We used transformation-associated recombination yeast directly clone and express an orphan biosynthetic cluster for lipopeptide antibiotic taromycin A. With this direct cloning approach, single genomic capture expression...