title: Chemical scaffolds with structural similarities to siderophores of nonribosomal peptide-polyketide origin as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis.
abstract: Mycobacterium tuberculosis (Mtb) and Yersinia pestis (Yp) produce siderophores with scaffolds of nonribosomal peptide-polyketide origin. Compounds with structural similarities to these siderophores were synthesized and evaluated as antimicrobials against Mtb and Yp under iron-limiting conditions mimicking the iron scarcity these pathogens encounter in the host and under standard iron-rich conditions. Several new antimicrobials were identified, including some with increased potency in the iron-limiting condition. Our study illustrates the possibility of screening compound libraries in both iron-rich and iron-limiting conditions to identify antimicrobials that may selectively target iron scarcity-adapted bacteria and highlights the usefulness of building combinatorial libraries of compounds having scaffolds with structural similarities to siderophores to feed into antimicrobial screening programs.
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Ferreras
authors.forename: Akash
authors.initials: A
authors.lastname: Gupta
authors.forename: Neal D
authors.initials: ND
authors.lastname: Amin
authors.forename: Arijit
authors.initials: A
authors.lastname: Basu
authors.forename: Barij N
authors.initials: BN
authors.lastname: Sinha
authors.forename: Stefan
authors.initials: S
authors.lastname: Worgall
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
authors.forename: Luis E N
authors.initials: LE
authors.lastname: Quadri
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D061065:Polyketides / Q000737:chemistry* / Q000494:pharmacology*; D017262:Siderophores / Q000737:chemistry*; D015010:Yersinia pestis / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D061065:Polyketides; D017262:Siderophores