A5017112785- Complement system in diseases
- Antimicrobial Resistance in Staphylococcus
- Biochemical and Structural Characterization
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood groups and transfusion
- Streptococcal Infections and Treatments
- Erythrocyte Function and Pathophysiology
- Immune Response and Inflammation
- Virus-based gene therapy research
- Bacterial Infections and Vaccines
- Bacterial biofilms and quorum sensing
- Viral gastroenteritis research and epidemiology
- Hemoglobinopathies and Related Disorders
- Clostridium difficile and Clostridium perfringens research
- Pneumocystis jirovecii pneumonia detection and treatment
- Nitric Oxide and Endothelin Effects
- Inflammation biomarkers and pathways
- RNA Interference and Gene Delivery
- Medical and Biological Ozone Research
- Antimicrobial Peptides and Activities
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Bacterial Identification and Susceptibility Testing
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Herpesvirus Infections and Treatments
- Neonatal Respiratory Health Research
Children's Hospital of The King's Daughters
2014-2024
Children's Specialty Group
2014-2024
Eastern Virginia Medical School
2015-2024
Enzo Life Sciences (United States)
2023
Pediatrics and Genetics
2014
Christie's
2010
Trinity College Dublin
2009
Duke Medical Center
1999-2004
Duke University Hospital
1999-2003
Virginia Commonwealth University Medical Center
1996
The purpose of the study was to examine risk factors for nosocomial pneumonia in surgical and medical/respiratory intensive care unit (ICU) populations. In a public teaching hospital, all cases ICUs (n = 20, respectively) were identified by prospective surveillance during 5-yr period from 1987-1991. Each group ICU compared with 40 control patients who did not acquire pneumonia, analyzed 25 potential factors. Surgical found have consistently higher rates than medical (RR 2.2). strongest...
ABSTRACT The human complement system is important in the immunological control of Staphylococcus aureus infection. We showed previously that S. surface protein clumping factor A (ClfA), when expressed recombinant form, bound I and increased cleavage C3b to iC3b. In present study, we show that, compared results for wild type, isogenic ClfA-deficient mutants were incubated serum, they less I, generated iC3b on bacterial surface, fewer C3 fragments. It has been shown two amino acids ClfA (P 336...
Similar to other highly successful invasive bacterial pathogens, Staphylococcus aureus recruits the complement regulatory protein factor H (fH) its surface inhibit alternative pathway of complement. Here, we report identification surface-associated SdrE as a fH-binding using purified fH overlay S. fractionated cell wall proteins and cross-linking followed by mass spectrometry. Studies recombinant revealed that rSdrE bound significant whether from serum or form, in both time- dose-dependent...
Complement-mediated opsonization of bacteria by C3 binding is an important component the host innate immune system. Little information available concerning interaction between complement proteins and capsule type 5 8 Staphylococcus aureus strains, even though these isolates are responsible for approximately 70% human staphylococcal infections. To investigate importance intact pathway in experimental infection, control C3-depleted mice were challenged intravenously with 10(7) CFU a serotype...
The human complement system plays an important role in the control of Staphylococcus aureus infection. For instance, we previously demonstrated that central component deposited on organism's surface, C3b, can be cleaved by host protein, factor I, resulting diminished phagocytosis S. aureus. In present study, have identified clumping A (ClfA) from cell wall proteins as a specific protein bound I. Recombinant ClfA (rClfA) containing full-length region (peptides 40-559) also We 50-kDa fragment...
ABSTRACT Human astroviruses (HAstVs) belong to a family of nonenveloped, icosahedral RNA viruses that cause noninflammatory gastroenteritis, predominantly in infants. Eight HAstV serotypes have been identified, with worldwide distribution. While the HAstVs represent significant public health concern, very little is known about pathogenesis and host immune response these viruses. Here we demonstrate type 1 (HAstV-1) virions, specifically viral coat protein (CP), suppress complement system,...
Abstract Background Diabetic patients are at increased risk for bacterial infections; these studies provide new insight into the role of host defense complement system in controlling pathogens hyperglycemic environments. Methods The interactions C3 with bacteria elevated glucose were assayed activation to opsonic forms, phagocytosis and killing. was analyzed euglycemic conditions by mass spectrometry measure glycation structural differences. Results Elevated inhibited S. aureus deposition...
Two major aspects of Systemic Lupus Erythematosus (SLE) pathogenesis that have yet to be targeted therapeutically are immune complex-initiated complement activation and neutrophil extracellular trap (NET) formation by neutrophils. Here we report in vitro testing Peptide Inhibitor Complement C1 (PIC1) assays complex-mediated human sera for NET The lead PIC1 derivative, PA-dPEG24, was able dose-dependently inhibit initiated multiple types complexes, including C1-antiC1q limiting the generation...
Abstract Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are completely understood. Human and murine vaccine studies support a role Abs in protecting against recurring infections, but S. modulates the B cell response through expression of staphylococcus protein A (SpA), surface drives polyclonal expansion induces death absence costimulation. In this study, we show SpA altered fate plasmablasts plasma cells (PCs) by enhancing short-lived...
ABSTRACT Complement-mediated opsonization of encapsulated Staphylococcus aureus (CP+) the predominant capsule types, 5 and 8, remains poorly understood. Our previous work showed that complement is important for mouse survival CP+ type bacteremia inhibits binding opsonic C3 fragments to organism. The importance complement-mediated was tested by neutrophil phagocytosis assays. increased 57% compared in complement-inhibited serum. Agar-grown CP+, enhancing expression, phagocytosed only...
Hyperglycemia from diabetes is associated with increased risk of infection S. aureus and severity illness. Previous work in our laboratory demonstrated that elevated glucose (>6 mM) dramatically inhibited aureus-initiated complement-mediated immune effectors. Here we report vivo studies evaluating the extent to which a hyperglycemic environment alters control rat peritonitis model. Rats were treated streptozocin induce or sham-treated then inoculated i.p. aureus. euthanized had peritoneal...
ABSTRACT Complement-mediated opsonization of Staphylococcus aureus bearing the dominant capsule serotypes, serotypes 5 and 8, remains incompletely understood. We have previously shown that complement plays a vital role in efficient phagocytosis serotype S. strain opsonic fragments central protein C3, C3b iC3b, were present on bacterial surface after incubation human serum. In studies, iC3b found several 8 strains Using purified classical activation pathway proteins Western blot assay, we...
We tested in vitro hypochlorite (bleach) killing of community-associated methicillin-resistant Staphylococcus aureus isolates to determine optimal concentration and duration. For all maximal killing, >3-log decrease colony forming units (CFU), was found after 5 minutes 2.5 microL/mL bleach. estimate that bleach is approximately one-half cup one-quarter tub water.
The complement system has been increasingly recognized to play a pivotal role in variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators the classical, lectin alternative pathways are currently pre-clinical clinical development. Our laboratory identified peptide that specifically inhibits classical is referred as Peptide Inhibitor Complement C1 (PIC1). In this study, we determined lead PIC1 variant demonstrates salt-dependent binding C1q, initiator molecule...
In cystic fibrosis (CF), lung damage is mediated by a cycle of obstruction, infection, inflammation and tissue destruction. The complement system major mediator for many diseases with the effectors C5a C3a often playing important roles. We have previously shown in small pilot study that CF sputum soluble fraction concentrations were associated clinical measures disease. Here we report much larger 34 subjects providing 169 testable samples allowing longitudinal evaluation comparing markers....
Staphylococcus aureus is a premier human pathogen and the most common cause of osteoarticular, wound, implanted device infections. We recently demonstrated S. efficiently binds classical complement regulator C4b-binding protein (C4BP) inhibiting antibody-initiated complement-mediated opsonization. Here we identify surface SdrE as C4BP-binding protein. Recombinant recombinant bone sialoprotein-binding (Bbp), an allelic variant SdrE, both bound to C4BP in heat-inactivated serum. previously...
Diabetic non-healing wounds are a major clinical problem. The mechanisms leading to poor wound healing in diabetes multifactorial but unresolved inflammation may be contributing factor. complement system (CS) is the most potent inflammatory cascade humans and contributes animal models. Signal transducer activator of transcription 4 (STAT4) factor expressed immune adipose cells upregulation some chemokines cytokines. Persistent CS STAT4 expression diabetic thus contribute chronic delayed...