Please use this identifier to cite or link to this item: http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/7684
Title: Heterocyclic Diaryliodonium-Based Inhibitors of Carbapenem-Resistant Acinetobacter baumannii
Authors: KUMARI, POOJA
Kaul, Grace
KUMAR, T. ANAND
Akhir, Abdul
Shukla, Manjulika
SHARMA, SURAJ
KAMAT, SIDDHESH S.
Chopra, Sidharth
CHAKRAPANI, HARINATH
Dept. of Biology
Dept. of Chemistry
Keywords: Biology
2023-MAR-WEEK4
TOC-MAR-2023
2023
Issue Date: Apr-2023
Publisher: American Society for Microbiology
Citation: Microbiology Spectrum, 11(02).
Abstract: Finding new therapeutic strategies against Gram-negative pathogens such as Acinetobacter baumannii is challenging. Starting from diphenyleneiodonium (dPI) salts, which are moderate Gram-positive antibacterials, we synthesized a focused heterocyclic library and found a potent inhibitor of patient-derived multidrug-resistant Acinetobacter baumannii strains that significantly reduced bacterial burden in an animal model of infection caused by carbapenem-resistant Acinetobacter baumannii (CRAB), listed as a priority 1 critical pathogen by the World Health Organization. Next, using advanced chemoproteomics platforms and activity-based protein profiling (ABPP), we identified and biochemically validated betaine aldehyde dehydrogenase (BetB), an enzyme that is involved in the metabolism and maintenance of osmolarity, as a potential target for this compound. Together, using a new class of heterocyclic iodonium salts, a potent CRAB inhibitor was identified, and our study lays the foundation for the identification of new druggable targets against this critical pathogen.
URI: https://doi.org/10.1128/spectrum.04773-22
http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/7684
ISSN: 2165-0497
Appears in Collections:JOURNAL ARTICLES

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