A5034101434- Immune Response and Inflammation
- Antimicrobial Resistance in Staphylococcus
- Bacterial biofilms and quorum sensing
- SARS-CoV-2 and COVID-19 Research
- Neonatal Respiratory Health Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pediatric health and respiratory diseases
- Inhalation and Respiratory Drug Delivery
- Clostridium difficile and Clostridium perfringens research
- COVID-19 Clinical Research Studies
- Gut microbiota and health
- Respiratory viral infections research
- Antimicrobial Peptides and Activities
- Wound Healing and Treatments
- Orthopedic Infections and Treatments
- Antibiotic Resistance in Bacteria
- Diabetic Foot Ulcer Assessment and Management
- Respiratory Support and Mechanisms
- Pneumonia and Respiratory Infections
- Virus-based gene therapy research
- Cystic Fibrosis Research Advances
- Nosocomial Infections in ICU
- Liver Disease Diagnosis and Treatment
- S100 Proteins and Annexins
- Streptococcal Infections and Treatments
AstraZeneca (United States)
2019-2025
Children's Hospital at Montefiore
2021
Pfizer (United Kingdom)
2021
Roche (Switzerland)
2021
Merck (Germany)
2021
Polyphor (Switzerland)
2021
Microbiotix (United States)
2021
Yale University
2021
GlaxoSmithKline (Brazil)
2021
Shionogi (Japan)
2021
Staphylococcus aureus USA300 strains cause a highly inflammatory necrotizing pneumonia. The virulence of this strain has been attributed to its expression multiple toxins that have diverse targets including ADAM10, NLRP3 and CD11b. We demonstrate induction necroptosis through RIP1/RIP3/MLKL signaling is major consequence S. toxin production. Cytotoxicity could be prevented by inhibiting either RIP1 or MLKL mutants lacking agr, hla Hla pore formation, lukAB psms were deficient in inducing...
The respiratory tract is exceptionally well defended against infection from inhaled bacteria, with multiple proinflammatory signaling cascades recruiting phagocytes to clear airway pathogens. However, organisms that efficiently activate damaging innate immune responses, such as those mediated by the inflammasome and caspase-1, may cause pulmonary damage interfere bacterial clearance. extracellular, opportunistic pathogen Pseudomonas aeruginosa expresses not only pathogen-associated molecular...
We observe previously unknown interactions between clinically important adenovirus vector capsids, platelet factor 4, and CAR.
Rapid deformation of brain matter caused by skull acceleration is most likely the cause concussion, as well more severe traumatic injury (TBI). The inability to measure directly has led disagreement and confusion about biomechanics concussion TBI. In present study, in human volunteers was measured during mild, but rapid, deceleration head (20–30 m/sec2 peak, ∼40 msec duration), using an imaging technique originally developed cardiac deformation. Magnetic resonance image sequences with...
Evolutionary biologists have postulated that several fitness advantages may be conferred by the maintenance of duplicate genes, including environmental adaptation resulting from differential regulation. We examined expression and physiological contributions two redundant operons in adaptable bacterium Pseudomonas aeruginosa PA14. These operons, phzA1-G1 (phz1) phzA2-G2 (phz2), encode nearly identical sets proteins catalyze synthesis phenazine-1-carboxylic acid, precursor for phenazine...
S. aureus α toxin promotes opportunistic co-infection, which can be neutralized with a pathogen-specific antibody.
Much of the morbidity and mortality associated with influenza virus respiratory infection is due to bacterial coinfection pathogens that colonize upper tract such as methicillin-resistant Staphylococcus aureus (MRSA) Streptococcus pneumoniae. A major component immune response production type I III interferons. Here we show causes an increase restructuring microbiota in wild-type (WT) mice but not Il28r(-/-) mutant lacking receptor for interferon. Mice IL-28 fail induce STAT1 phosphorylation...
The trans-fat containing AMLN (amylin liver non-alcoholic steatohepatitis, NASH) diet has been extensively validated in C57BL/6J mice with or without the Lepob/Lepob (ob/ob) mutation leptin gene for reliably inducing metabolic and histopathological changes recapitulating hallmarks of NASH. Due to a recent ban on trans-fats as food additive, there is marked need developing new capable promoting compatible level disease ob/ob mice.To develop biopsy-confirmed mouse model NASH based an...
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in variants that can escape neutralization by therapeutic antibodies. Here, we describe AZD3152, a SARS-CoV-2–neutralizing monoclonal antibody designed to provide improved potency and coverage against emerging variants. AZD3152 binds the back left shoulder SARS-CoV-2 spike protein receptor binding domain prevents interaction with human angiotensin-converting enzyme receptor. potently neutralized broad...
The type III interferon (IFNλ) receptor IL-28R is abundantly expressed in the respiratory tract and has been shown essential for host defense against some viral pathogens, however no data are available concerning its role innate immune response to bacterial pathogens. Staphylococcus aureus Pseudomonas aeruginosa induced significant production of IFNλ lung, clearance these bacteria from lung was significantly increased null mice compared controls. Improved correlated with reduced pathology a...
Highlights•Alpha toxin activates the inflammasome, preventing bacterial clearance•NLRP3 activation, not downstream cytokine production, leads to impaired defense•Macrophage NLRP3 activation sequesters mitochondria away from internalized S. aureus•Mitochondrial ROS is required for caspase-1 and killing in macrophagesSummaryClinical severity of Staphylococcus aureus respiratory infection correlates with alpha (AT) expression. AT inflammasome; deletion Nlrp3, or neutralization, protects mice...
Neutrophils are critical for the defense against pathogens, in part through extrusion of extracellular DNA traps, phagocytosis, and production reactive oxygen species. may also play an important role pathogenesis rheumatoid arthritis (RA) activation protein arginine deiminases (PADs) that citrullinate proteins subsequently act as autoantigens. We report PAD4 is physically associated with cytosolic subunits oxidative burst machinery, p47phox (also known neutrophil cytosol factor 1, NCF1)...
Significance Hematogenous implant-related infections are an important clinical problem because bacteria spread from the bloodstream to a previously well-functioning implant and result in infectious complications failure of medical device or prosthesis. To study these infections, we developed preclinical animal model Staphylococcus aureus hematogenous infection with capability monitor noninvasively longitudinally dissemination blood surgically placed orthopedic implant. Using this model,...
Immunocompromised individuals are at increased risk of Staphylococcus aureus pneumonia. Neutralization alpha-toxin (AT) with the monoclonal antibody (MAb) MEDI4893* protects normal mice from S. pneumonia; however, effects MAb in immunocompromised have not been reported. In this study, passive immunization survival rates and reduced bacterial numbers lungs an murine pneumonia model. Lungs infected exhibited alveolar epithelial damage, protein leakage, overgrowth, whereas passively immunized...
Staphyococcus aureus and especially the epidemic methicillin-resistant S. strains cause severe necrotizing pneumonia. The mechanisms whereby these organisms invade across mucosal epithelial barrier to initiate invasive infection are not well understood. Protein A (SpA), a highly conserved abundant surface protein of aureus, activates TNF receptor 1 EGF (EGFR) signaling cascades that can perturb cytoskeleton. We demonstrate wild-type but spa mutants, polarized airway cell monolayers via...
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Staphylococcus aureus wound infections delay healing and result in invasive complications such as osteomyelitis, especially the setting of diabetic foot ulcers. In preclinical animal models S. skin infection, antibody neutralization alpha-toxin (AT), an aureus-secreted pore-forming cytolytic toxin, reduces disease severity by inhibiting necrosis restoring effective host immune responses. However, whether therapeutic is against aureus-infected wounds unclear. Herein, efficacy prophylactic...
Neutrophils abandon infection control during wound repair.