Author:
Lun Shichun,Guo Haidan,Adamson John,Cisar Justin S.,Davis Tony D.,Chavadi Sivagami Sundaram,Warren J. David,Quadri Luis E. N.,Tan Derek S.,Bishai William R.
Abstract
ABSTRACTMycobactin biosynthesis inMycobacterium tuberculosisfacilitates iron acquisition, which is required for growth and virulence. The mycobactin biosynthesis inhibitor salicyl-AMS [5′-O-(N-salicylsulfamoyl)adenosine] inhibitsM. tuberculosisgrowthin vitrounder iron-limited conditions. Here, we conducted a single-dose pharmacokinetic study and a monotherapy study of salicyl-AMS with mice. Intraperitoneal injection yielded much better pharmacokinetic parameter values than oral administration did. Monotherapy of salicyl-AMS at 5.6 or 16.7 mg/kg significantly inhibitedM. tuberculosisgrowth in the mouse lung, providing the firstin vivoproof of concept for this novel antibacterial strategy.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
47 articles.
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