Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 2 of 2
Full-Text Articles in Lipids
Targeting Lipoprotein Biogenesis: Considerations Towards Antimicrobials, Toufic El Arnaout, Tewfic Soulimane
Targeting Lipoprotein Biogenesis: Considerations Towards Antimicrobials, Toufic El Arnaout, Tewfic Soulimane
Articles
Decades have passed without approval of a new antibiotic class. Several companies have recently halted related discovery efforts because of multiple obstacles. One promising route under research is to target the lipoprotein maturation pathway in light of major recent findings and the virulence roles of lipoproteins. To support the future design of selective drugs, considerations and priority-setting are established for the main lipoprotein processing enzymes (Lgt, LspA, and Lnt) based on microbiology, biochemistry, structural biology, chemical design, and pharmacology. Although not all bacterial species will be similarly impacted by drug candidates, several advantages make LspA a top target to pursue …
Cardiolipin Prevents Membrane Translocation And Permeabilization By Daptomycin, Tianhua Zhang, Jawad K. Muraih, Nasim Tishbi, Jennifer Herskowitz, Rachel L. Victor, Jared Silverman, Stephanie Uwumarenogie, Scott D. Taylor, Michael Palmer, Evan Mintzer
Cardiolipin Prevents Membrane Translocation And Permeabilization By Daptomycin, Tianhua Zhang, Jawad K. Muraih, Nasim Tishbi, Jennifer Herskowitz, Rachel L. Victor, Jared Silverman, Stephanie Uwumarenogie, Scott D. Taylor, Michael Palmer, Evan Mintzer
Lander College of Arts and Sciences Publications and Research
Daptomycin is an acidic lipopeptide antibiotic that, in the presence of calcium, forms oligomeric pores on membranes containing phosphatidylglycerol. It is clinically used against various Gram-positive bacteria such as Staphylococcus aureus and Enterococcusspecies. Genetic studies have indicated that an increased content of cardiolipin in the bacterial membrane may contribute to bacterial resistance against the drug. Here, we used a liposome model to demonstrate that cardiolipin directly inhibits membrane permeabilization by daptomycin. When cardiolipin is added at molar fractions of 10 or 20% to membranes containing phosphatidylglycerol, daptomycin no longer forms pores or translocates to the inner membrane leaflet. Under …