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Enterotoxigenic Escherichia coli (ETEC) is a prevalent cause of traveler's diarrhea and infant mortality in third-world countries. Heat-labile enterotoxin (LT) is secreted from ETEC via vesicles composed of outer membrane and periplasm. We investigated the role of ETEC vesicles in pathogenesis by analyzing vesicle association and entry into eukaryotic(More)
Outer membrane vesicles (OMVs) are produced by all Gram-negative microorganisms studied to date. The contributions of OMVs to biological processes are diverse and include mediation of bacterial stress responses, selective packaging and secretion of virulence determinants, modulation of the host immune response, and contributions to biofilm formation and(More)
Bacteria have evolved strategies to resist killing by antimicrobial peptides (APs), important effectors of innate immunity. The sap (sensitivity to antimicrobial peptides) operon confers resistance to AP-mediated killing of Salmonella. We have recently shown that sapA gene expression is upregulated in the middle ear in a chinchilla model of nontypeable(More)
Bacterial strategies of innate immune evasion and essential metabolic functions are critical for commensal-host homeostasis. Previously, we showed that Sap translocator function is necessary for nontypeable Haemophilus influenzae (NTHI) behaviors that mediate diseases of the human airway. Antimicrobial peptide (AP) lethality is limited by binding mediated(More)
Nontypeable Haemophilus influenzae (NTHi) is a leading causative agent of otitis media. Much of the inflammation occurring during NTHi disease is initiated by lipooligosaccharides (LOS) on the bacterial surface. Phosphorylcholine (PCho) is added to some LOS forms in a phase-variable manner, and these PCho(+) variants predominate in vivo. Thus, we asked(More)
The gram-negative bacterium nontypeable Haemophilus influenzae (NTHI) is the predominant pathogen in chronic otitis media with effusion and, with Streptococcus pneumoniae and Moraxella catarrhalis, is a causative agent of acute otitis media. To identify potential virulence determinants, bacterial gene expression was monitored by differential fluorescence(More)
We have shown that non-typeable Haemophilus influenzae (NTHI) resists killing by antimicrobial peptides (APs). A mutant defective in expression of the sap (sensitivity to antimicrobial peptides) gene cluster product SapA is sensitive to killing by APs and is significantly attenuated in its ability to survive in a chinchilla model of otitis media compared(More)
Cigarette smoking continues to place an enormous burden on US health systems. The treatment of tobacco-dependent persons is vital to the public health, since unmitigated smoking could lead to the development of disease and premature death in as many as 20 million current smokers in the United States. Much of this tobacco-related morbidity and mortality(More)
Antimicrobial peptides (AMPs) contribute to host innate immune defense and are a critical component to control bacterial infection. Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharyngeal mucosa, yet is commonly associated with opportunistic infections of the upper and lower respiratory tracts. An important aspect of(More)
We have developed a novel co-culture system in which murine splenocytes are cultured with live bacteria in the presence of a bacteriostatic antibiotic. Superantigens, like staphylococcal enterotoxin B (SEB) are important factors in bacterial pathogenicity. Research has shown that superantigens affect numerous immune cell types, either directly or(More)