In vitro and in silico screening of Klebsiella pneumoniae new Delhi metallo-β-lactamase-1 inhibitors from endophytic Streptomyces spp. Issue 24 (26th December 2022)

• Record Type: Journal Article
• Authors: Cheepurupalli, Lalitha; Diaz, Aathithya; Gopal, Adithya Conjeevaram; Rathore, Sudarshan Singh; Ramakrishnan, Vigneshwar; Ramakrishnan, Jayapradha
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 24(2022)
• Page Start: 13593
• Page End: 13605
• Publication Date: 2022-12-26
• Subjects: β-lactamase inhibitors -- Streptomyces spp. -- drug resistance -- molecular interactions; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.1990132
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: The increase in drug resistance over the last two decades is a big threat in health care settings. More importantly, the dissemination of carbapenem-resistant Enterobacteriaceae is the major threat to public health with an increase in morbidity and mortality. β-lactamase is known to confer enteric bacteria with nearly complete resistance to all β-lactam antibiotics including the late-generation carbapenems. The commercially available β-lactamase inhibitors, clavulanic acid, sulbactam, and tazobactam are being met with an increasing number of resistant phenotypes and are ineffective against pathogens harbouring New Delhi metallo- β -lactamase (NDM-1). Inhibition of New Delhi metallo- β -lactamase-1 activity is one potential way to treat metallo β-lactamase (MBL) producing multi drug resistant (MDR) pathogen. The present study focused on screening of Klebsiella pneumoniae New Delhi metallo- β -lactamase-1 (BLIs) from endophytic Streptomyces spp. using in vitro and in silico methods. The study identified three potential inhibitors of New Delhi metallo- β -lactamase-1, namely dodecanoic acid, dl -alanyl- l -leucine and phenyl propanedioic acid. These molecules were found to bind to other MBLs namely, IMP-1 and VIM-2. To the best of our knowledge, this is the first kind of study reporting the binding mode of these molecules with New Delhi metallo- β -lactamase-1. Communicated by Ramaswamy H. Sarma