grC binding. A more quantitative measure of the competition was obtained with the P3-blaZ reporter strain exposed to a fixed concentration of Solonamide B and dilutions of the spent supernatant from stationary phase, wild type cells. The results show that 50% inhibition was reached 7 Solonamide B Inhibits Agr of S. aureus when challenged 2578618 in all the specificity groups, as measured by P3 activity, with the least effect towards agr group III. alpha-type PSMs. Importantly, when bacterial cells were cultured in the presence of Solonamide B there was a dramatic effect on psma expression as the presence of the compound essentially abolished expression in both strain 8325-4 and USA300. To assess if this effect is correlated with agrA expression we probed the agr P2 transcript with a probe covering agrA and found it to be significantly decreased in both strains but most so in USA300. Thus, the reduced expression of psma is likely caused by reduced expression of agrA. Solonamide B Reduces PSM Expression and Neutrophil Killing Neutrophils are a part of the innate immune system, and as the first leukocytes that infiltrate affected tissues they are one of the primary defenses against Staphylococcal infection. S. aureus produces PSMs of which the alpha type PSM is the most important for neutrophil lysis, with PSMa3 having the most pronounced effect. Since our transcriptional analysis revealed that Solonamide B dramatically reduces expression of psma we examined if it 
may be protective of S. aureus mediated neutrophil killing. To this end we monitored toxicity of sterile filtered CA-MRSA USA300 supernatant grown with and without Solonamide B on h
Posted inUncategorized