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Identification of Specific and Nonspecific Inhibitors of Bacillus anthracis Type?III Pantothenate Kinase (PanK).

ABSTRACT: Antibiotics with novel mechanisms of action are desperately needed to combat the increasing rates of multidrug-resistant infections. Bacterial pantothenate kinase (PanK) has emerged as a target of interest to cut off the biosynthesis of coenzyme?A. Herein we report the results of an in vitro high-throughput screen of over 10?000 small molecules against Bacillus anthracis PanK, as well as a follow-up screen of hits against PanK isolated from Pseudomonas aeruginosa and Burkholderia cenocepacia. Nine hits are structurally categorized and analyzed to set the stage for future drug development.

SUBMITTER: Shapiro JA

PROVIDER: S-EPMC6456334 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Identification of Specific and Nonspecific Inhibitors of Bacillus anthracis Type III Pantothenate Kinase (PanK).

Shapiro Justin A JA Varga John J JJ Parsonage Derek D Walton William W Redinbo Matthew R MR Ross Larry J LJ White E Lucile EL Bostwick Robert R Wuest William M WM Claiborne Al A Goldberg Joanna B JB

ChemMedChem 20181203 1

Antibiotics with novel mechanisms of action are desperately needed to combat the increasing rates of multidrug-resistant infections. Bacterial pantothenate kinase (PanK) has emerged as a target of interest to cut off the biosynthesis of coenzyme A. Herein we report the results of an in vitro high-throughput screen of over 10 000 small molecules against Bacillus anthracis PanK, as well as a follow-up screen of hits against PanK isolated from Pseudomonas aeruginosa and Burkholderia cenocepacia. Ni ...[more]

PMID: 30376607

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The type III pantothenate kinase encoded by coaX is essential for growth of Bacillus anthracis.

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