A5035963839- Antimicrobial Resistance in Staphylococcus
- Antimicrobial Peptides and Activities
- Immune Response and Inflammation
- Biotin and Related Studies
- Bacterial biofilms and quorum sensing
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Enzyme Structure and Function
- Biochemical and Structural Characterization
- Streptococcal Infections and Treatments
- Mosquito-borne diseases and control
- Air Quality and Health Impacts
- Biochemical and biochemical processes
- Asthma and respiratory diseases
- RNA and protein synthesis mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Toxin Mechanisms and Immunotoxins
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bacteriophages and microbial interactions
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Neurological diseases and metabolism
- Psychosomatic Disorders and Their Treatments
- Bacterial Identification and Susceptibility Testing
- Metabolism and Genetic Disorders
- Drug-Induced Adverse Reactions
University of New Mexico
2013-2024
Engineering Service Center und Handel (Germany)
2013
Veterans Health Administration
2008-2013
New Mexico VA Health Care System
2010-2013
National Institute of Pathology
2007
National Institute of Diabetes and Digestive and Kidney Diseases
2005-2006
National Institutes of Health
2005-2006
National Cancer Institute
2005
Case Western Reserve University
2002-2004
University School
2004
Innate immunity is the first line of defense against invading pathogens. Toll-like receptors (TLRs) act as sentinels innate immune system, sensing a variety ligands from lipopolysaccharide to flagellin dsRNA through their ligand-binding domain that composed leucine-rich repeats (LRRs). Ligand binding initiates signaling cascade leads up-regulation inflammation mediators. In this study, we have expressed and crystallized ectodomain (ECD) human TLR3, which recognizes dsRNA, molecular signature...
Bacterial signaling systems are prime drug targets for combating the global health threat of antibiotic resistant bacterial infections including those caused by Staphylococcus aureus. S. aureus is primary cause acute skin and soft tissue (SSTIs) quorum sensing operon agr causally associated with these. Whether efficacious chemical inhibitors can be developed that promote host defense against SSTIs while sparing normal microbiota unknown. In a high throughput screen, we identified small...
Pathogen recognition by Toll-like receptors (TLRs) initiates innate immune responses that are essential for inhibiting pathogen dissemination and the development of acquired immunity. The TLRs recognize pathogens with their N-terminal ectodomains (ECD), but molecular basis this is not known. Recently we reported x-ray structure unliganded TLR3-ECD; however, it has proven difficult to obtain a crystal TLR3 its ligand, dsRNA. We have now located ligand binding site mutational analysis. More...
Air pollution is implicated in neurodegenerative disease risk and progression microglial activation, but the mechanisms are unknown. In this study, microglia remained activated 24 h after ozone (O3) exposure rats, suggesting a persistent signal from lung to brain. Ex vivo analysis of serum O3-treated rats revealed an augmented proinflammatory response β-amyloid 42 (Aβ42) neurotoxicity independent traditional circulating cytokines, where macrophage-1 antigen-mediated priming. Aged mice...
Significance Inhaled particulates, such as multiwalled carbon nanotubes, can induce neuroinflammatory outcomes. The present study shows that acute neuroinflammation is dependent on the impairment of blood-brain barrier function. Pharmacologic restoration integrity prevented responses to pulmonary nanotube exposure. Circulating factors, including possibly thrombospondin-1, recapitulate inflammatory in cultured cerebrovascular endothelial cells, suggesting a mechanism for indirect systemic...
Antibiotic-resistant pathogens are a global health threat. Small molecules that inhibit bacterial virulence have been suggested as alternatives or adjuncts to conventional antibiotics, they may limit pathogenesis and increase susceptibility host killing. Staphylococcus aureus is major cause of invasive skin soft tissue infections (SSTIs) in both the hospital community settings, it also becoming increasingly antibiotic resistant. Quorum sensing (QS) mediated by accessory gene regulator (agr)...
Greater than 20% of cases and 0.4% deaths from COVID-19 occur in children. Following demonstration the safety efficacy adjuvanted, recombinant spike protein vaccine NVX-CoV2373 adults, PREVENT-19 trial immediately expanded to adolescents.
ABSTRACT Vancomycin (VAN) is often used to treat methicillin-resistant Staphylococcus aureus (MRSA) bacteremia despite a high incidence of microbiological failure. Recent in vitro analyses β-lactams combination with VAN demonstrated synergistic activity against MRSA. The goal this study was examine the impact therapy and β-lactam (Combo) on eradication MRSA compared alone. This retrospective cohort patients who received Combo or Microbiological MRSA, defined as negative blood culture...
Inhaled pollutants induce the release of vasoactive factors into systemic circulation, but little information is available regarding nature these or their receptors. The pattern recognition receptor CD36 interacts with many damage-related circulating molecules, leading to activation endothelial cells and promoting vascular inflammation; therefore, we hypothesized that plays a pivotal role in mediating cross talk between inhaled ozone (O3)-induced dysfunction. O3 exposure (1 ppm × 4h) induced...
Hantaviruses indigenous to the New World are etiologic agents of hantavirus cardiopulmonary syndrome (HCPS). These viruses induce a strong interferon-stimulated gene (ISG) response in human endothelial cells. African green monkey-derived Vero E6 cells used propagate hantaviruses as well many other viruses. The utility cell line for virus production is thought owe their lack genes encoding type I interferons (IFN), rendering them unable mount an efficient innate immune infection. Interferon...
During a screen of the Nebraska Transposon Mutant Library, we identified 71 mutations in Staphylococcus aureus genome that altered hemolysis on blood agar medium. Although many these disrupted genes known to affect production alpha-hemolysin, two them were associated with an apparent operon, designated vfrAB, had not been characterized previously. Interestingly, ΔvfrB mutant exhibited only minor effects transcription hla gene, encoding when grown broth, as well RNAIII, posttranscriptional...
Staphylococcus aureus contains an autoinducing quorum-sensing system encoded within the agr operon that coordinates expression of virulence genes required for invasive infection. Allelic variation has generated four specific groups, I–IV, each which secretes a distinct peptide pheromone (AIP1-4) drives signaling. Because signaling mediates phenotypic change in this pathogen from adherent colonizing phenotype to one associated with considerable tissue injury and invasiveness, we postulated...
Inhalation of multiwalled carbon nanotubes (MWCNT) causes systemic effects including vascular inflammation, endothelial dysfunction, and acute phase protein expression. MWCNTs translocate only minimally beyond the lungs, thus cardiovascular thereof may be caused by generation secondary biomolecular factors from MWCNT-pulmonary interactions that spill over into circulation. Therefore, we hypothesized induced matrix metalloproteinase-9 (MMP-9) is a generator that, in turn, drive through...
Glutathione S-transferases (GSTs) are a major family of detoxification enzymes which possess wide range substrate specificities. Most organisms many GSTs belonging to multiple classes. Interest in insects is focused on their role insecticide resistance; resistant have elevated levels GST activity. In the malaria vector Anopheles gambiae, associated with resistance organochlorine DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane]. This mosquito source an insect GST, agGSTd1-6, metabolizes...
Abstract Sin Nombre virus (SNV) is a highly pathogenic New World and etiologic agent of hantavirus cardiopulmonary syndrome. We have previously shown that replication-defective particles are able to induce strong IFN-stimulated gene (ISG) response in human primary cells. RNA viruses often stimulate the innate immune by interactions between viral nucleic acids, acting as pathogen-associated molecular pattern, cellular pattern-recognition receptors (PRRs). Ligand binding PRRs activates...
Abstract Numerous studies have reported sex bias in infectious diseases, with direction dependent on pathogen and site of infection. Staphylococcus aureus is the most common cause skin soft tissue infections (SSTIs), yet susceptibility to S. SSTI has not been described. A search electronic health records revealed an odds ratio 2.4 for males versus females. To investigate physiological basis this bias, we compared outcomes between male female mice a model dermonecrosis. Consistent...
ABSTRACT A major shortcoming to plasmid-based genetic tools is the necessity of using antibiotics ensure plasmid maintenance. While selectable markers are very powerful, their use not always practical, such as during in vivo models bacterial infection. During previous studies, it was noted that uncharacterized LAC-p01 Staphylococcus aureus USA300 isolates stable absence a known selection and therefore could serve platform for new species. genetically manipulated into an Escherichia coli - S....
Sex bias in innate defense against Staphylococcus aureus skin and soft tissue infection (SSTI) is dependent on both estrogen production by the host S. secretion of virulence factor, α-hemolysin (Hla). The impact signaling immune system most often studied terms nuclear receptors ERα ERβ. However, potential contribution G protein-coupled receptor (GPER) to infectious disease, particularly with respect infection, has not been addressed. Using a murine model SSTI, we found that GPER activation...
Staphylococcus aureus is an opportunistic, pathogenic bacteria that causes significant morbidity and mortality. As antibiotic resistance by S. continues to be a serious concern, developing novel drug therapies combat these infections vital. Quorum sensing inhibitors (QSI) dampen virulence facilitate clearance the host immune system blocking quorum signaling promotes upregulation of genes controlled accessory gene regulator (agr) operon. While QSIs have shown therapeutic promise in mouse...
Abstract Staphylococcus aureus is the primary cause of skin and structure infections (SSSIs) in United States. α-Hemolysin (Hla), a pore-forming toxin secreted by S. major contributor to tissue necrosis, prompts recruitment neutrophils critical for host defense against infections. However, failure clear apoptotic can result damage tissues, suggesting that mechanisms neutrophil clearance are essential limiting Hla-mediated dermonecrosis. We hypothesized CD36, scavenger receptor which...
A major hurdle in vaccine development is the difficulty identifying relevant target epitopes and then presenting them to immune system a context that mimics their native conformation. We have engineered novel virus-like-particle (VLP) technology able display complex libraries of random peptide sequences on surface-exposed loop coat protein without disruption folding or VLP assembly. This allows us use same particle for both affinity selection immunization, integrating power epitope discovery...