- Pneumonia and Respiratory Infections
- Bacterial Infections and Vaccines
- Immune Response and Inflammation
- Streptococcal Infections and Treatments
- Antibiotic Resistance in Bacteria
- Respiratory viral infections research
- Bacterial Genetics and Biotechnology
- Pneumocystis jirovecii pneumonia detection and treatment
- Influenza Virus Research Studies
- Antimicrobial Peptides and Activities
- Escherichia coli research studies
- Antimicrobial Resistance in Staphylococcus
- RNA and protein synthesis mechanisms
- Neonatal Respiratory Health Research
- Pediatric health and respiratory diseases
- Glycosylation and Glycoproteins Research
- Antibiotics Pharmacokinetics and Efficacy
- Bacteriophages and microbial interactions
- Blood disorders and treatments
- Immunodeficiency and Autoimmune Disorders
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- S100 Proteins and Annexins
- Respiratory and Cough-Related Research
St. Jude Children's Research Hospital
2016-2025
Rockefeller University
1990-2015
Office of Infectious Diseases
2001-2013
European Molecular Biology Organization
2012-2013
Meyer (China)
2012-2013
John Wiley & Sons (United Kingdom)
2012-2013
University of Tennessee Health Science Center
1998-2006
University of Tennessee at Knoxville
2005-2006
Penn State Milton S. Hershey Medical Center
2005
Northwestern University
2005
Abstract Invasive infection with Gram-positive and Gram-negative bacteria often results in septic shock death. The basis for the earliest steps innate immune response to bacterial is poorly understood. LPS component of cell wall appears activate cells via CD14 Toll-like receptor (TLR) 2 TLR4. We hypothesized that might also be recognized by TLRs. Heterologous expression human TLR2, but not TLR4, fibroblasts conferred responsiveness Staphylococcus aureus Streptococcus pneumoniae as evidenced...
NF-kappa B, a heterodimeric transcription factor composed of p50 and p65 subunits, can be activated in many cell types is thought to regulate wide variety genes involved immune function development. Mice lacking the subunit B show no developmental abnormalities, but exhibit multifocal defects responses involving lymphocytes nonspecific infection. cells do not proliferate response bacterial lipopolysaccharide are defective basal specific antibody production. unable effectively clear L....
Nongrowing bacteria evade the bactericidal activity of beta-lactam antibiotics. We sought to determine if slow growth rate also alters activity. The two beta-lactams on Escherichia coli grown in glucose limited chemostats was compared for generation times ranging from 0.7 12 h. degree killing varied with drug structure and E. strain. However, all rates were a constant function bacterial time: slowly growing became progressively more phenotypically tolerant antibiotics as time extended.
During the course of whooping cough, Bordetella pertussis interacts with alveolar macrophages and other leukocytes on respiratory epithelium. We report here mechanisms by which these bacteria adhere to human in vitro. Whole means two proteins, filamentous hemagglutinin (FHA) toxin, either is sufficient mediate adherence. FHA classes molecules macrophages, galactose-containing glycoconjugates integrin CR3 (αMβ2, ). The interaction between involves recognition Arg-Gly-Asp (RGD) sequence at...
Although Streptococcus pneumoniae is a major cause of meningitis in humans, the mechanisms underlying its traversal from circulation across blood-brain barrier (BBB) into subarachnoid space are poorly understood. One mechanism might involve transcytosis through microvascular endothelial cells. In this study we investigated ability pneumococci to invade and transmigrate monolayers rat human brain cells (BMEC). Significant variability was found invasive capacity clinical isolates. Phase...
Cytokines mediate many host responses to bacterial infections. We determined the inflammatory activities of five cytokines in central nervous system: TNF-alpha, IL-1 alpha, beta, macrophage protein 1 (MIP-1), and 2 (MIP-2). Using a rabbit model meningeal inflammation, each cytokine (except beta) induced enhanced blood brain barrier permeability, leukocytosis cerebrospinal fluid, edema. Homologous antibodies mediator inhibited edema, moderately decreased permeability. In rabbits treated with...
Journal Article The Induction of Meningeal Inflammation by Components the Pneumococcal Cell Wall Get access Elaine Tuomanen, Tuomanen Search for other works this author on: Oxford Academic PubMed Google Scholar Hans Liu, Liu Bruno Hengstler, Hengstler Oto Zak, Zak Alexander Tomasz Infectious Diseases, Volume 151, Issue 5, May 1985, Pages 859–868, https://doi.org/10.1093/infdis/151.5.859 Published: 01 1985 history Received: 17 September 1984 Revision received: 29 November
Filamentous hemagglutinin is a surface-associated adherence protein of Bordetella pertussis, which component some new acellular pertussis vaccines. The nucleotide sequence an open reading frame that encompasses the filamentous structural gene, fhaB, suggests proteolytic processing necessary to generate mature 220-kDa product. An Arg-Gly-Asp (RGD) tripeptide found within may be involved in its properties. internal in-frame deletion encompassing RGD region, causes loss B. pertussis-binding...
We tested if specific inhibition of recruitment leukocytes across the blood brain barrier from vascular compartment to cerebrospinal fluid (CSF) space reduced tissue damage and improved outcome infection in a rabbit model experimental meningitis. The CD11/CD18 complex receptors on promotes adhesion these cells endothelia, process required for egress into extravascular space. Intravenous injection anti-CD18 mAb IB4 effectively blocked development leukocytosis CSF animals challenged...
A diverse array of infectious agents, including prions and certain neurotropic viruses, bind to the laminin receptor (LR), this determines tropism CNS. Bacterial meningitis in childhood is almost exclusively caused by respiratory tract pathogens Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, but mechanism which they initiate contact with vascular endothelium blood brain barrier (BBB) unknown. We hypothesized that an interaction LR might underlie their CNS tropism....
Microbial targets for protective humoral immunity are typically surface-localized proteins and contain common sequence motifs related to their secretion or surface binding. Exploiting the whole genome of human bacterial pathogen Streptococcus pneumoniae, we identified 130 open reading frames encoding with similarity predicted virulence factors. Mice were immunized 108 these proteins, 6 conferred protection against disseminated S. pneumoniae infection. Flow cytometry confirmed localization...
Interleukin 12 (IL-12) strongly augments gamma interferon production by natural killer (NK) and T cells. IL-12 also promotes effective cell-mediated immune responses, which are particularly important against intracellular bacteria such as Listeria monocytogenes. While the lipopolysaccharide (LPS) of gram-negative induces monocyte IL-12, relevant gram-positive components induce uncharacterized. We used human monocytic cell line THP-1 to study induction bacteria. Muramyl dipeptides well major...
We assessed the ability of Streptococcus pneumoniae mutants deficient in either choline binding protein A (CbpA), pneumolysin (Pln), pyruvate oxidase (SpxB), autolysin (LytA), pneumococcal surface A, or neuraminidase (NanA) to replicate distinct anatomical sites and translocate from one site next. Intranasal, intratracheal, intravenous models disease were 4-week-old BALB/cJ mice by quantitation bacterial titers relevant organs. Mice also observed use real-time bioluminescent imaging (BLI)....
Pneumococcus is the most common and aggressive cause of bacterial meningitis induces a novel apoptosis-inducing factor–dependent (AIF–dependent) form brain cell apoptosis. Loss production two pneumococcal toxins, pneumolysin H2O2, eliminated mitochondrial damage Purified or H2O2 induced microglial neuronal apoptosis in vitro. Both toxins increases intracellular Ca2+ triggered release AIF from mitochondria. Chelating effectively blocked death. In experimental meningitis, colocalized with...
ABSTRACT The choline binding proteins (CBPs) are a family of surface noncovalently bound to the phosphorylcholine moiety cell wall Streptococcus pneumoniae by conserved domain. Six new members this were identified, and these six plus two recently described hydrolases, LytB LytC, characterized for their roles in virulence. CBP-deficient mutants constructed tested adherence eukaryotic cells, colonization rat nasopharynx, ability cause sepsis. Five CBP mutants, CbpD, CbpE, CbpG, LytB, showed...