Chemical scaffolds with structural similarities to siderophores of nonribosomal peptide-polyketide origin as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis |
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Authors: | Ferreras Julian A Gupta Akash Amin Neal D Basu Arijit Sinha Barij N Worgall Stefan Jayaprakash Venkatesan Quadri Luis E N |
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Affiliation: | Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA. |
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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. |
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Keywords: | Nonribosomal peptide Polyketide Siderophore Mycobacterium tuberculosis Yersinia pestis Antimicrobial compound Pyrazoline Hydroxyhydrazine |
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