Siderophore Conjugates of Daptomycin are Potent Inhibitors of Carbapenem Resistant Strains of Acinetobacter baumannii.
Development of resistance to antibiotics is a major medical problem. One approach to extending the utility of our limited antibiotic arsenal is to repurpose antibiotics by altering their bacterial selectivity. Many antibiotics that are used to treat infections caused by Gram-positive bacteria might be made effective against Gram-negative bacterial infections, if they could circumvent permeability barriers and antibiotic deactivation processes associated with Gram-negative bacteria. Herein, we report that covalent attachment of the normally Gram-positive-only antibiotic, daptomycin, with iron sequestering siderophore mimetics that are recognized by Gram-negative bacteria, provides conjugates that are active against virulent strains of Acinetobacter baumannii, including carbapenemase and cephalosporinase producers. The result is the generation of a new set of antibiotics designed to target bacterial infections that have been designated as being of dire concern.
['Ghosh|Manuka|M|', 'Lin|Yun-Ming|YM|', 'Miller|Patricia A|PA|', 'Möllmann|Ute|U|', 'Boggess|William C|WC|', 'Miller|Marvin J|MJ|0000-0002-3704-8214']
D040981:Acinetobacter baumannii D000900:Anti-Bacterial Agents D015780:Carbapenems D017576:Daptomycin D055808:Drug Discovery D024901:Drug Resistance, Multiple, Bacterial D005296:Ferrous Compounds D006094:Gram-Positive Bacteria D006801:Humans D008826:Microbial Sensitivity Tests D010455:Peptides D011485:Protein Binding D017262:Siderophores D065093:beta-Lactamase Inhibitors
siderophore conjugate daptomycin antibiotic Gram-negative sideromycin