Screening and identification of phytochemicals from Acorus calamus L. to overcome NDM-1 mediated resistance in Klebsiella pneumoniae using in silico approach

Klebsiella pneumoniae is a potent human pathogen and a prevalent ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Considerably, K. pneumoniae becomes a major clinical problem due to numerous AMR ge...

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Main Authors: Janki V. Rojmala, Anjali B. Thakkar, Dhruti Joshi, Bhargav N. Waghela, Parth Thakor
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024162421
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author Janki V. Rojmala
Anjali B. Thakkar
Dhruti Joshi
Bhargav N. Waghela
Parth Thakor
author_facet Janki V. Rojmala
Anjali B. Thakkar
Dhruti Joshi
Bhargav N. Waghela
Parth Thakor
author_sort Janki V. Rojmala
collection DOAJ
description Klebsiella pneumoniae is a potent human pathogen and a prevalent ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Considerably, K. pneumoniae becomes a major clinical problem due to numerous AMR genes [extended-spectrum β-lactamase, plasmid-mediated AmpC, carbapenemases, tigecycline resistance, and New Delhi Metallo-β-lactamase-1 (NDM-1)] and can hydrolyze the majority of β-lactam antibiotics. Hence, targeting NDM-1 could be an effective approach to eradicate K. pneumoniae pathogenesis. A plethora of reports suggests that the plant compounds possess an anti-microbial activity and their utilization could be a promising strategy to develop novel antibiotics. Our study utilized the hydromethanolic leaves extract of Acorus calamus L. (AC) to target NDM-1 containing K. pneumonia using an in silico approach. At first, we determined the phytochemical composition of AC using GC-HRMS. Further, the phytoconstituents were screened against the NDM-1 (PDB ID: 3ZR9) of K. pneumoniae through molecular docking studies. Our results revealed the compounds from AC such as (2R,4S,6R,7S,8R,9S,13S)-16-hydroxy-5′,7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icos-1(12)-ene-6,2′-oxane]-11-one (−9.5 kcal/mol), 4,4,5,8-tetramethyl-2,3-dihydrochromen-2-ol (−6.6 kcal/mol), 5-chloro-2-(2,4-dichloro phenoxy)phenol (−6.0 kcal/mol), [(3S,3aS,6R,6aS)-3-nitrooxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate (−5.7 kcal/mol), 4-(3-hydroxyprop-1-enyl)-2-methoxyphenol (−5.6 kcal/mol), and (E)-3-(2,4-dimethoxyphenyl)prop-2-enoic acid (−5.6 kcal/mol) possess substantial docking scores against NDM-1. Therefore, our study concludes that phytochemicals of AC may inhibit NDM-1-mediated resistance in K. pneumoniae and could be an alternative therapeutic strategy for targeting NDM-1-containing K. pneumoniae.
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spelling doaj-art-7613b337635e4b08946d0778d74908822025-08-20T02:07:34ZengElsevierHeliyon2405-84402024-11-011022e4021110.1016/j.heliyon.2024.e40211Screening and identification of phytochemicals from Acorus calamus L. to overcome NDM-1 mediated resistance in Klebsiella pneumoniae using in silico approachJanki V. Rojmala0Anjali B. Thakkar1Dhruti Joshi2Bhargav N. Waghela3Parth Thakor4Department of Microbiology, Atmiya University, Kalawad Road, Rajkot, Gujarat, IndiaPost Graduate Department of Biosciences, Satellite Campus, Sardar Patel University, Vallabhvidyanagar, Gujarat, IndiaDepartment of Microbiology, Atmiya University, Kalawad Road, Rajkot, Gujarat, IndiaDepartment of Microbiology, Atmiya University, Kalawad Road, Rajkot, Gujarat, India; Corresponding author.Bapubhai Desaibhai Patel Institute of Paramedical Sciences, Charotar University of Science and Technology, Changa, Gujarat, India; Corresponding author. Bapubhai Desaibhai Patel Institute of Paramedical Sciences, CHARUSAT, Changa, Gujrat, India.Klebsiella pneumoniae is a potent human pathogen and a prevalent ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Considerably, K. pneumoniae becomes a major clinical problem due to numerous AMR genes [extended-spectrum β-lactamase, plasmid-mediated AmpC, carbapenemases, tigecycline resistance, and New Delhi Metallo-β-lactamase-1 (NDM-1)] and can hydrolyze the majority of β-lactam antibiotics. Hence, targeting NDM-1 could be an effective approach to eradicate K. pneumoniae pathogenesis. A plethora of reports suggests that the plant compounds possess an anti-microbial activity and their utilization could be a promising strategy to develop novel antibiotics. Our study utilized the hydromethanolic leaves extract of Acorus calamus L. (AC) to target NDM-1 containing K. pneumonia using an in silico approach. At first, we determined the phytochemical composition of AC using GC-HRMS. Further, the phytoconstituents were screened against the NDM-1 (PDB ID: 3ZR9) of K. pneumoniae through molecular docking studies. Our results revealed the compounds from AC such as (2R,4S,6R,7S,8R,9S,13S)-16-hydroxy-5′,7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icos-1(12)-ene-6,2′-oxane]-11-one (−9.5 kcal/mol), 4,4,5,8-tetramethyl-2,3-dihydrochromen-2-ol (−6.6 kcal/mol), 5-chloro-2-(2,4-dichloro phenoxy)phenol (−6.0 kcal/mol), [(3S,3aS,6R,6aS)-3-nitrooxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate (−5.7 kcal/mol), 4-(3-hydroxyprop-1-enyl)-2-methoxyphenol (−5.6 kcal/mol), and (E)-3-(2,4-dimethoxyphenyl)prop-2-enoic acid (−5.6 kcal/mol) possess substantial docking scores against NDM-1. Therefore, our study concludes that phytochemicals of AC may inhibit NDM-1-mediated resistance in K. pneumoniae and could be an alternative therapeutic strategy for targeting NDM-1-containing K. pneumoniae.http://www.sciencedirect.com/science/article/pii/S2405844024162421Klebsiella pneumoniaeMDRNDM-1β-lactamAcorus calamus L
spellingShingle Janki V. Rojmala
Anjali B. Thakkar
Dhruti Joshi
Bhargav N. Waghela
Parth Thakor
Screening and identification of phytochemicals from Acorus calamus L. to overcome NDM-1 mediated resistance in Klebsiella pneumoniae using in silico approach
Heliyon
Klebsiella pneumoniae
MDR
NDM-1
β-lactam
Acorus calamus L
title Screening and identification of phytochemicals from Acorus calamus L. to overcome NDM-1 mediated resistance in Klebsiella pneumoniae using in silico approach
title_full Screening and identification of phytochemicals from Acorus calamus L. to overcome NDM-1 mediated resistance in Klebsiella pneumoniae using in silico approach
title_fullStr Screening and identification of phytochemicals from Acorus calamus L. to overcome NDM-1 mediated resistance in Klebsiella pneumoniae using in silico approach
title_full_unstemmed Screening and identification of phytochemicals from Acorus calamus L. to overcome NDM-1 mediated resistance in Klebsiella pneumoniae using in silico approach
title_short Screening and identification of phytochemicals from Acorus calamus L. to overcome NDM-1 mediated resistance in Klebsiella pneumoniae using in silico approach
title_sort screening and identification of phytochemicals from acorus calamus l to overcome ndm 1 mediated resistance in klebsiella pneumoniae using in silico approach
topic Klebsiella pneumoniae
MDR
NDM-1
β-lactam
Acorus calamus L
url http://www.sciencedirect.com/science/article/pii/S2405844024162421
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