Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis.

Objectives: Pseudomonas aeruginosa is the most common pathogen in the bronchiectasis lung, associated with worsened outcomes. P. aeruginosa genomic studies in this context have been limited to single-country, European studies.

Exposure of Escherichia coli to antibiotic-efflux pump inhibitor combinations in a pharmacokinetic model: impact on bacterial clearance and drug resistance.

Background: Efflux pump inhibitors (EPIs) offer an attractive therapeutic option when combined with existing classes. However, their optimal dosing strategies are unknown.

Methods: MICs of ciprofloxacin (CIP)+/-chlorpromazine, phenylalanine-arginine β naphthylamide (PAβN) and a developmental molecule MBX-4191 were determined and the pharmacodynamics (PD) was studied in an in vitro model employing Escherichia coli MG1655 and its isogenic MarR mutant (I1147).

Chlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux Pump.

Efflux is an important mechanism in Gram-negative bacteria conferring multidrug resistance. Inhibition of efflux is an encouraging strategy to restore the antibacterial activity of antibiotics. Chlorpromazine and amitriptyline have been shown to behave as efflux inhibitors.

The effect of lipidation and glycosylation on short cationic antimicrobial peptides.

The global health threat surrounding bacterial resistance has resulted in antibiotic researchers shifting their focus away from 'traditional' antibiotics and concentrating on other antimicrobial agents, including antimicrobial peptides. These low molecular weight "mini-proteins" exhibit broad-spectrum activity against bacteria, including multi-drug resistant strains, viruses, fungi and protozoa and constitute a major element of the innate-immune system of many multicellular organisms. Some naturally occurring antimicrobial peptides are lipidated and/or glycosylated and almost all antimicrobial peptides in clinical use are either lipopeptides (Daptomycin and Polymyxin E and B) or glycopeptides (Vancomycin).

Overexpression of RamA, Which Regulates Production of the Multidrug Resistance Efflux Pump AcrAB-TolC, Increases Mutation Rate and Influences Drug Resistance Phenotype.

In , the AcrAB-TolC efflux pump exports substrates, including antimicrobials, from the cell. Overexpression of AcrAB-TolC can occur after exposure to fluoroquinolones, leading to multidrug resistance. The expression of AcrAB-TolC in is primarily regulated by the transcriptional activator RamA.

Do phenothiazines possess antimicrobial and efflux inhibitory properties?

Antibiotic resistance is a global health concern; the rise of drug-resistant bacterial infections is compromising the medical advances that resulted from the introduction of antibiotics at the beginning of the 20th century. Considering that the presence of mutations within individuals in a bacterial population may allow a subsection to survive and propagate in response to selective pressure, as long as antibiotics are used in the treatment of bacterial infections, development of resistance is an inevitable evolutionary outcome. This, combined with the lack of novel antibiotics being released to the clinical market, means the need to develop alternative strategies to treat these resistant infections is critical.

Temperature sensitive point mutations in fission yeast tropomyosin have long range effects on the stability and function of the actin-tropomyosin copolymer.

The actin cytoskeleton is modulated by regulatory actin-binding proteins which fine-tune the dynamic properties of the actin polymer to regulate function. One such actin-binding protein is tropomyosin (Tpm), a highly-conserved alpha-helical dimer which stabilises actin and regulates interactions with other proteins. Temperature sensitive mutants of Tpm are invaluable tools in the study of actin filament dependent processes, critical to the viability of a cell.

Screening and Optimizing Antimicrobial Peptides by Using SPOT-Synthesis.

Peptide arrays on cellulose are a powerful tool to investigate peptide interactions with a number of different molecules, for examples antibodies, receptors or enzymes. Such peptide arrays can also be used to study interactions with whole cells. In this review, we focus on the interaction of small antimicrobial peptides with bacteria.