Brilacidin (PMX30063) has shown potent bactericidal activity against drug-resistant and susceptible strains of multiple Gram negative and Gram positive pathogens. In this study, we demonstrate that brilacidin causes membrane depolarization in the gram-positive bacterium Staphylococcus aureus, to an extent comparable to that caused by the lipopeptidic drug, daptomycin. Transcriptional profiling of Staphylococcus aureus by deep-sequencing shows that the global response to brilacidin treatment is well-correlated to that of treatment with daptomycin and the cationic antimicrobial peptide, LL37, and mostly indicates abrogation of cell-wall and membrane function. Furthermore, the upregulation of various chaperones and proteases by brilacidin and daptomycin indicates cytoplasmic protein misfolding stress could be a contributor to the mechanism of action of these drugs. These stress responses were mainly orchestrated by three two-component systems: GraSR, VraSR and NsaSR, which have been implicated in virulence and drug resistance against other clinically available antibiotics.
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Saw this posted on another Message board. Go CTIX!
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