Gallic Acid: A Potent Metabolite Targeting Shikimate Kinase in Acinetobacter baumannii
is a highly multidrug-resistant pathogen resistant to almost all classes of antibiotics; new therapeutic strategies against this infectious agent are urgently needed. Shikimate kinase is an enzyme belonging to the shikimate pathway and has become a potential target for drug development. This work de...
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creator | Alturki, Mansour S Al Khzem, Abdulaziz H Gomaa, Mohamed S Tawfeeq, Nada Alhamadah, Marwah H Alshehri, Futun M Alzahrani, Raghad Alghamdi, Hanin Rants'o, Thankhoe A Ayil, Khaled A G Al Mouslem, Abdulaziz K Almaghrabi, Mohammed |
description | is a highly multidrug-resistant pathogen resistant to almost all classes of antibiotics; new therapeutic strategies against this infectious agent are urgently needed. Shikimate kinase is an enzyme belonging to the shikimate pathway and has become a potential target for drug development. This work describes the search for Food and Drug Administration (FDA)-approved drugs and natural compounds, including gallic acid, that could be repurposed as selective shikimate kinase inhibitors by integrated computational and experimental approaches.
Approaches to drug design using structure-based and ligand-based methodology, in-silico screening, molecular docking, and molecular dynamics for the study of both binding affinity and stability. Experimental Validation Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) on
and
.
Among them, gallic acid, obtained from plants, proved to be the most promising compound that showed sufficient binding with shikimate kinase through computational studies. Gallic acid showed very good activity against
and
in the MIC and MBC assay, respectively. Gallic acid exhibited better activity against
due to the overexpression of shikimate kinase. Gallic acid has emerged as a potential therapeutic candidate drug against
infection and, therefore, as a strategy against the appearance of multidrug-resistant microorganisms. This study not only identifies a novel repurposing opportunity for gallic acid but also provides a comprehensive computational and experimental framework for accelerating antimicrobial drug discovery against multidrug-resistant pathogens. |
doi_str_mv | 10.3390/metabo14120727 |
format | Article |
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Approaches to drug design using structure-based and ligand-based methodology, in-silico screening, molecular docking, and molecular dynamics for the study of both binding affinity and stability. Experimental Validation Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) on
and
.
Among them, gallic acid, obtained from plants, proved to be the most promising compound that showed sufficient binding with shikimate kinase through computational studies. Gallic acid showed very good activity against
and
in the MIC and MBC assay, respectively. Gallic acid exhibited better activity against
due to the overexpression of shikimate kinase. Gallic acid has emerged as a potential therapeutic candidate drug against
infection and, therefore, as a strategy against the appearance of multidrug-resistant microorganisms. This study not only identifies a novel repurposing opportunity for gallic acid but also provides a comprehensive computational and experimental framework for accelerating antimicrobial drug discovery against multidrug-resistant pathogens.</description><identifier>ISSN: 2218-1989</identifier><identifier>EISSN: 2218-1989</identifier><identifier>DOI: 10.3390/metabo14120727</identifier><identifier>PMID: 39728508</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Accuracy ; Acinetobacter baumannii ; Antibiotics ; Antimicrobial agents ; Binding sites ; Computer applications ; Drug development ; Drug resistance ; Enterococcus faecalis ; Enzymes ; FDA approval ; Flexibility ; Gallic acid ; Hydrogen bonds ; Kinases ; Ligands ; Metabolites ; Minimum inhibitory concentration ; Molecular dynamics ; molecular simulation ; Mortality ; Multidrug resistance ; Nosocomial infections ; Pathogens ; Penicillin ; Pneumonia ; Proteins ; Shikimate kinase ; Simulation ; Ventilators</subject><ispartof>Metabolites, 2024-12, Vol.14 (12), p.727</ispartof><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0001-7702-9379 ; 0000-0003-4929-7071 ; 0000-0001-8585-0888 ; 0000-0002-3868-2057 ; 0000-0003-2112-9092 ; 0009-0004-0079-8646 ; 0000-0002-9178-9021</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11677302/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11677302/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39728508$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alturki, Mansour S</creatorcontrib><creatorcontrib>Al Khzem, Abdulaziz H</creatorcontrib><creatorcontrib>Gomaa, Mohamed S</creatorcontrib><creatorcontrib>Tawfeeq, Nada</creatorcontrib><creatorcontrib>Alhamadah, Marwah H</creatorcontrib><creatorcontrib>Alshehri, Futun M</creatorcontrib><creatorcontrib>Alzahrani, Raghad</creatorcontrib><creatorcontrib>Alghamdi, Hanin</creatorcontrib><creatorcontrib>Rants'o, Thankhoe A</creatorcontrib><creatorcontrib>Ayil, Khaled A G</creatorcontrib><creatorcontrib>Al Mouslem, Abdulaziz K</creatorcontrib><creatorcontrib>Almaghrabi, Mohammed</creatorcontrib><title>Gallic Acid: A Potent Metabolite Targeting Shikimate Kinase in Acinetobacter baumannii</title><title>Metabolites</title><addtitle>Metabolites</addtitle><description>is a highly multidrug-resistant pathogen resistant to almost all classes of antibiotics; new therapeutic strategies against this infectious agent are urgently needed. Shikimate kinase is an enzyme belonging to the shikimate pathway and has become a potential target for drug development. This work describes the search for Food and Drug Administration (FDA)-approved drugs and natural compounds, including gallic acid, that could be repurposed as selective shikimate kinase inhibitors by integrated computational and experimental approaches.
Approaches to drug design using structure-based and ligand-based methodology, in-silico screening, molecular docking, and molecular dynamics for the study of both binding affinity and stability. Experimental Validation Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) on
and
.
Among them, gallic acid, obtained from plants, proved to be the most promising compound that showed sufficient binding with shikimate kinase through computational studies. Gallic acid showed very good activity against
and
in the MIC and MBC assay, respectively. Gallic acid exhibited better activity against
due to the overexpression of shikimate kinase. Gallic acid has emerged as a potential therapeutic candidate drug against
infection and, therefore, as a strategy against the appearance of multidrug-resistant microorganisms. This study not only identifies a novel repurposing opportunity for gallic acid but also provides a comprehensive computational and experimental framework for accelerating antimicrobial drug discovery against multidrug-resistant pathogens.</description><subject>Accuracy</subject><subject>Acinetobacter baumannii</subject><subject>Antibiotics</subject><subject>Antimicrobial agents</subject><subject>Binding sites</subject><subject>Computer applications</subject><subject>Drug development</subject><subject>Drug resistance</subject><subject>Enterococcus faecalis</subject><subject>Enzymes</subject><subject>FDA approval</subject><subject>Flexibility</subject><subject>Gallic acid</subject><subject>Hydrogen bonds</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Metabolites</subject><subject>Minimum inhibitory concentration</subject><subject>Molecular dynamics</subject><subject>molecular simulation</subject><subject>Mortality</subject><subject>Multidrug resistance</subject><subject>Nosocomial infections</subject><subject>Pathogens</subject><subject>Penicillin</subject><subject>Pneumonia</subject><subject>Proteins</subject><subject>Shikimate kinase</subject><subject>Simulation</subject><subject>Ventilators</subject><issn>2218-1989</issn><issn>2218-1989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNpdkU1rFTEUhoMottRuXcqAGzdX8zFnkriRS9FarChY3YaTj3ub60zSZjKC_970tkprCEk4efPwcELIc0ZfC6HpmylUtJn1jFPJ5SNyyDlTK6aVfnzvfECO53lH2xgoSMqekgOhJVdA1SH5cYrjGF23dtG_7dbd11xDqt3nPXmMNXQXWLahxrTtvl3Gn3HCVvsUE86hi-nmXQo1W3Q1lM7iMmFKMT4jTzY4zuH4bj8i3z-8vzj5uDr_cnp2sj5feU4HvnLe2Z565QEUCMcR7OC0Aie19QP1iLBBwSH40KsNYxQALYXBBwkeLBNH5OyW6zPuzFVpeuW3yRjNvpDL1mCp0Y3BKIdUDhvnqaY9BKmbAHPaCqbbtNhY725ZV4udgnetDwXHB9CHNylemm3-ZRgbpBSUN8KrO0LJ10uYq5ni7MI4Ygp5mY1gvYYeKNyIv_wvustLSa1X-9Sg2got9eK-0j-Xv_8n_gD8p51_</recordid><startdate>20241223</startdate><enddate>20241223</enddate><creator>Alturki, Mansour S</creator><creator>Al Khzem, Abdulaziz H</creator><creator>Gomaa, Mohamed S</creator><creator>Tawfeeq, Nada</creator><creator>Alhamadah, Marwah H</creator><creator>Alshehri, Futun M</creator><creator>Alzahrani, Raghad</creator><creator>Alghamdi, Hanin</creator><creator>Rants'o, Thankhoe A</creator><creator>Ayil, Khaled A G</creator><creator>Al Mouslem, Abdulaziz K</creator><creator>Almaghrabi, Mohammed</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>7QR</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-7702-9379</orcidid><orcidid>https://orcid.org/0000-0003-4929-7071</orcidid><orcidid>https://orcid.org/0000-0001-8585-0888</orcidid><orcidid>https://orcid.org/0000-0002-3868-2057</orcidid><orcidid>https://orcid.org/0000-0003-2112-9092</orcidid><orcidid>https://orcid.org/0009-0004-0079-8646</orcidid><orcidid>https://orcid.org/0000-0002-9178-9021</orcidid></search><sort><creationdate>20241223</creationdate><title>Gallic Acid: A Potent Metabolite Targeting Shikimate Kinase in Acinetobacter baumannii</title><author>Alturki, Mansour S ; Al Khzem, Abdulaziz H ; Gomaa, Mohamed S ; Tawfeeq, Nada ; Alhamadah, Marwah H ; Alshehri, Futun M ; Alzahrani, Raghad ; Alghamdi, Hanin ; Rants'o, Thankhoe A ; Ayil, Khaled A G ; Al Mouslem, Abdulaziz K ; Almaghrabi, Mohammed</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-d2062-cdcb40d8d55853c2a5b6c985c79bd60daa5fa325ede48f11055ab056de75d5b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Accuracy</topic><topic>Acinetobacter baumannii</topic><topic>Antibiotics</topic><topic>Antimicrobial agents</topic><topic>Binding sites</topic><topic>Computer applications</topic><topic>Drug development</topic><topic>Drug resistance</topic><topic>Enterococcus faecalis</topic><topic>Enzymes</topic><topic>FDA approval</topic><topic>Flexibility</topic><topic>Gallic acid</topic><topic>Hydrogen bonds</topic><topic>Kinases</topic><topic>Ligands</topic><topic>Metabolites</topic><topic>Minimum inhibitory concentration</topic><topic>Molecular dynamics</topic><topic>molecular simulation</topic><topic>Mortality</topic><topic>Multidrug resistance</topic><topic>Nosocomial infections</topic><topic>Pathogens</topic><topic>Penicillin</topic><topic>Pneumonia</topic><topic>Proteins</topic><topic>Shikimate kinase</topic><topic>Simulation</topic><topic>Ventilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alturki, Mansour S</creatorcontrib><creatorcontrib>Al Khzem, Abdulaziz H</creatorcontrib><creatorcontrib>Gomaa, Mohamed S</creatorcontrib><creatorcontrib>Tawfeeq, Nada</creatorcontrib><creatorcontrib>Alhamadah, Marwah H</creatorcontrib><creatorcontrib>Alshehri, Futun M</creatorcontrib><creatorcontrib>Alzahrani, Raghad</creatorcontrib><creatorcontrib>Alghamdi, Hanin</creatorcontrib><creatorcontrib>Rants'o, Thankhoe A</creatorcontrib><creatorcontrib>Ayil, Khaled A G</creatorcontrib><creatorcontrib>Al Mouslem, Abdulaziz K</creatorcontrib><creatorcontrib>Almaghrabi, Mohammed</creatorcontrib><collection>PubMed</collection><collection>Chemoreception Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Metabolites</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alturki, Mansour S</au><au>Al Khzem, Abdulaziz H</au><au>Gomaa, Mohamed S</au><au>Tawfeeq, Nada</au><au>Alhamadah, Marwah H</au><au>Alshehri, Futun M</au><au>Alzahrani, Raghad</au><au>Alghamdi, Hanin</au><au>Rants'o, Thankhoe A</au><au>Ayil, Khaled A G</au><au>Al Mouslem, Abdulaziz K</au><au>Almaghrabi, Mohammed</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gallic Acid: A Potent Metabolite Targeting Shikimate Kinase in Acinetobacter baumannii</atitle><jtitle>Metabolites</jtitle><addtitle>Metabolites</addtitle><date>2024-12-23</date><risdate>2024</risdate><volume>14</volume><issue>12</issue><spage>727</spage><pages>727-</pages><issn>2218-1989</issn><eissn>2218-1989</eissn><abstract>is a highly multidrug-resistant pathogen resistant to almost all classes of antibiotics; new therapeutic strategies against this infectious agent are urgently needed. Shikimate kinase is an enzyme belonging to the shikimate pathway and has become a potential target for drug development. This work describes the search for Food and Drug Administration (FDA)-approved drugs and natural compounds, including gallic acid, that could be repurposed as selective shikimate kinase inhibitors by integrated computational and experimental approaches.
Approaches to drug design using structure-based and ligand-based methodology, in-silico screening, molecular docking, and molecular dynamics for the study of both binding affinity and stability. Experimental Validation Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) on
and
.
Among them, gallic acid, obtained from plants, proved to be the most promising compound that showed sufficient binding with shikimate kinase through computational studies. Gallic acid showed very good activity against
and
in the MIC and MBC assay, respectively. Gallic acid exhibited better activity against
due to the overexpression of shikimate kinase. Gallic acid has emerged as a potential therapeutic candidate drug against
infection and, therefore, as a strategy against the appearance of multidrug-resistant microorganisms. This study not only identifies a novel repurposing opportunity for gallic acid but also provides a comprehensive computational and experimental framework for accelerating antimicrobial drug discovery against multidrug-resistant pathogens.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39728508</pmid><doi>10.3390/metabo14120727</doi><orcidid>https://orcid.org/0000-0001-7702-9379</orcidid><orcidid>https://orcid.org/0000-0003-4929-7071</orcidid><orcidid>https://orcid.org/0000-0001-8585-0888</orcidid><orcidid>https://orcid.org/0000-0002-3868-2057</orcidid><orcidid>https://orcid.org/0000-0003-2112-9092</orcidid><orcidid>https://orcid.org/0009-0004-0079-8646</orcidid><orcidid>https://orcid.org/0000-0002-9178-9021</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Accuracy Acinetobacter baumannii Antibiotics Antimicrobial agents Binding sites Computer applications Drug development Drug resistance Enterococcus faecalis Enzymes FDA approval Flexibility Gallic acid Hydrogen bonds Kinases Ligands Metabolites Minimum inhibitory concentration Molecular dynamics molecular simulation Mortality Multidrug resistance Nosocomial infections Pathogens Penicillin Pneumonia Proteins Shikimate kinase Simulation Ventilators |
title | Gallic Acid: A Potent Metabolite Targeting Shikimate Kinase in Acinetobacter baumannii |
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