Entry of Burkholderia organisms into respiratory epithelium: CFTR, microfilament and microtubule dependence.

Background: The pathogenesis of infection with Burkholderia cepacia complex (Bcc) organisms may be linked to its capacity to invade respiratory epithelium.

Methods: An antibiotic exclusion assay was used to study B. dolosa AU4459 and B.

In vitro and murine efficacy and toxicity studies of nebulized SCC1, a methylated caffeine-silver(I) complex, for treatment of pulmonary infections.

The expanding clinical challenge of respiratory tract infections due to resistant bacteria necessitates the development of new forms of therapy. The development of a compound composed of silver coupled to a methylated caffeine carrier (silver carbene complex 1 [SCC1]) that demonstrated in vitro efficacy against bacteria, including drug-resistant organisms, isolated from patients with respiratory tract infections was described previously. The findings of current in vitro studies now suggest that bactericidal concentrations of SCC1 are not toxic to airway epithelial cells in primary culture.

Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus aureus clearance.

Background: Staphylococcus aureus is the most common cause of healthcare-associated pneumonia. Despite the significant morbidity and mortality associated with the disease, animal models of S. aureus pneumonia are rare.

Synthesis, stability, and antimicrobial studies of electronically tuned silver acetate N-heterocyclic carbenes.

A series of methylated imidazolium salts with varying substituents on the 4 and 5 positions of the imidazole ring were synthesized. These salts were reacted with silver acetate to afford their corresponding silver N-heterocyclic carbene (NHC) complexes. These complexes were then evaluated for their stability in water as well as for their antimicrobial efficacy against a variety of bacterial strains associated with cystic fibrosis and chronic lung infections.

Cathepsin-G interferes with clearance of Pseudomonas aeruginosa from mouse lungs.

The cystic fibrosis airway is susceptible to Pseudomonas aeruginosa infection, which stimulates an intense inflammatory response leading to airway obstruction and bronchiectasis. Neutrophils migrate into the airway, and once there, release high concentrations of neutral serine proteases during phagocytosis and in death. In particular, neutrophil elastase is central to progression of bronchiectasis by interfering with bacterial clearance and directly perpetuating the inflammatory response in the airway.

Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection.

Granulocyte colony-stimulating factor (G-CSF) regulates the production, maturation, and function of neutrophils. Its expression is often induced during infection, resulting in high concentrations of G-CSF in inflammatory exudates and in the blood, suggesting that it may regulate both local and systemic neutrophil responses. Herein, we characterize the neutrophil response in G-CSFR(-/-) mice following intratracheal injection with Pseudomonas aeruginosa-laden agarose beads, modeling the pulmonary infection observed in many patients with cystic fibrosis.

Synthesis from caffeine of a mixed N-heterocyclic carbene-silver acetate complex active against resistant respiratory pathogens.

The bis(N-heterocyclic carbene) (NHC) silver complex, 3, with a methyl carbonate anion was formed from the reaction of the iodide salt of methylated caffeine, 1, with silver (I) oxide in methanol. Attempts to crystallize this complex from a mixture of common alcohols and ethyl acetate led to the formation of an NHC-silver acetate complex, 4. The more direct synthesis of 4 was accomplished by the in-situ deprotonation of 1 by silver acetate in methanol.

Imaging lung inflammation in a murine model of Pseudomonas infection: a positron emission tomography study.

We tested the hypothesis that the uptake of [18F]fluorodeoxyglucose (FDG), as measured by positron emission tomography (PET) imaging, would correlate with inflammation caused by increasing doses of instilled Pseudomonas aeruginosa (PA) into the lungs of mice. PA-laden agarose beads were instilled via the trachea into 1 lung of each mouse (dose range 0.5-15 x 10(4) CFU) and imaging was performed 3 days later (at the peak of the inflammatory response).