zithromax and homoserine-lactone

Pseudomonas aeruginosa is an opportunistic pathogen and a leading cause of nosocomial infections. Unfortunately, P. aeruginosa has low antibiotic susceptibility due to several chromosomally encoded antibiotic resistance genes. Hence, we carried out mechanistic studies to determine how azithromycin affects quorum sensing and virulence in P. aeruginosa. lasI and rhlI single and double mutants were constructed. We then undertook a quantitative approach to determine the optimal concentration of azithromycin and culture time that can affect the expression of HSLs. Furthermore, based on the above results, the effect on quorum sensing was analyzed at a transcriptional level. It was found that 2 μg/mL azithromycin caused a 79% decrease in 3-oxo-C12-HSL secretion during cultivation, while C4-HSL secretion was strongly repressed in the early stages. Azithromycin acts on ribosomes; to determine whether this can elicit alternative modes of gene expression, transcriptional regulation of representative virulence genes was analyzed. We propose a new relationship for lasI and rhlI: lasI acts as a cell density sensor, and rhlI functions as a fine-tuning mechanism for coordination between different quorum sensing systems.

Topics: 4-Butyrolactone; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Ligases; Pseudomonas aeruginosa; Quorum Sensing; Transcription Factors; Virulence

Topics: 4-Butyrolactone; Animals; Anti-Bacterial Agents; Apoptosis; Azithromycin; Bacterial Proteins; Cells, Cultured; Chemokine CCL2; Chemokine CXCL2; Chemokines; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Glycolipids; Macrophages; Mice; Pancreatic Elastase; Pseudomonas aeruginosa; Signal Transduction