Proteomic analysis of the adaptive responses of Pseudomonas aeruginosa to aminoglycoside antibiotics.

The opportunistic human pathogen, Pseudomonas aeruginosa, is a major cause of life-threatening infections in patients with cystic fibrosis. These infections are usually controlled through antibiotic intervention. In this study we use quantitative proteomic analysis to investigate how P.

Using chemical probes to investigate the sub-inhibitory effects of azithromycin.

The antibacterial drug azithromycin has clinically beneficial effects at sub-inhibitory concentrations for the treatment of conditions characterized by chronic Pseudomonas aeruginosa infection, such as cystic fibrosis. These effects are, in part, the result of inhibition of bacterial biofilm formation. Herein, the efficient synthesis of azithromycin in 4 steps from erythromycin and validation of the drug's ability to inhibit biofilm formation at sub-MIC (minimum inhibitory concentration) values are reported.

Variations on a theme: diverse N-acyl homoserine lactone-mediated quorum sensing mechanisms in gram-negative bacteria.

Many Gram-negative bacteria employ a mechanism of cell-cell communication known as quorum sensing (QS). The role of QS is to enable the cells in a culture to coordinate their gene expression profile with changes in the population cell density. The best characterized mechanisms of QS employ N-acylated homoserine lactones (AHLs) as signalling molecules.

Cell-cell communication in Gram-negative bacteria.

Over the last decade or so, a wealth of research has established that bacteria communicate with one another using small molecules. These signals enable the individuals in a population to coordinate their behaviour. In the case of pathogens, this behaviour may include decisions such as when to attack a host organism or form a biofilm.

Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain.

Abnormal phosphorylation of tau is a feature of Alzheimer's disease (AD), which develops prematurely in Down syndrome (DS) patients. Cognitive impairment is also recognized as a clinical characteristic of schizophrenia, which does not appear to be associated with tau-aggregate formation. Several kinases can phosphorylate tau in cell-free assays.

Fast biphasic regulation of type 3 inositol trisphosphate receptors by cytosolic calcium.

In cytosol-like medium (CLM) with a free [Ca(2+)] of 200 nm, a supramaximal concentration of inositol 1,4,5-trisphosphate (IP(3)) (30 microm) evoked (45)Ca(2+) release from type 3 IP(3) receptors only after a latency of 48 +/- 6 ms; this latency could not be reduced by increasing the IP(3) concentration. In CLM containing a low free [Ca(2+)] ( approximately 4 nm), 300 microm IP(3) evoked (45)Ca(2+) release after a latency of 66 +/- 11 ms; this was reduced to 14 +/- 3 ms when the [Ca(2+)] was 1 mm. Preincubation with CLM containing 100 microm Ca(2+) caused a rapid (half-time = 33 +/- 9 ms), complete, and fully reversible inhibition that could not be overcome by a high concentration of IP(3) (300 microm).