Antibacterial activity of menadione alone and in combination with oxacillin against methicillin-resistant Staphylococcus aureus and its impact on biofilms

Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial...

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Veröffentlicht in:Journal of medical microbiology 2023-01, Vol.72 (9)
Hauptverfasser: Leitão, Amanda Cavalcante, Ferreira, Thais Lima, Gurgel do Amaral Valente Sá, Lívia, Rodrigues, Daniel Sampaio, de Souza, Beatriz Oliveira, Barbosa, Amanda Dias, Moreira, Lara Elloyse Almeida, de Andrade Neto, João Batista, Cabral, Vitória Pessoa de Farias, Rios, Maria Erivanda França, Cavalcanti, Bruno Coêlho, Silva, Jacilene, Marinho, Emmanuel Silva, dos Santos, Hélcio Silva, de Moraes, Manoel Odorico, Júnior, Hélio Vitoriano Nobre, da Silva, Cecília Rocha
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container_issue 9
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container_title Journal of medical microbiology
container_volume 72
creator Leitão, Amanda Cavalcante
Ferreira, Thais Lima
Gurgel do Amaral Valente Sá, Lívia
Rodrigues, Daniel Sampaio
de Souza, Beatriz Oliveira
Barbosa, Amanda Dias
Moreira, Lara Elloyse Almeida
de Andrade Neto, João Batista
Cabral, Vitória Pessoa de Farias
Rios, Maria Erivanda França
Cavalcanti, Bruno Coêlho
Silva, Jacilene
Marinho, Emmanuel Silva
dos Santos, Hélcio Silva
de Moraes, Manoel Odorico
Júnior, Hélio Vitoriano Nobre
da Silva, Cecília Rocha
description Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents. Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress. Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis. Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity. Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml −1 , with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects. Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.
doi_str_mv 10.1099/jmm.0.001751
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Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents. Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress. Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis. Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity. Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml −1 , with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects. Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.</description><identifier>ISSN: 0022-2615</identifier><identifier>ISSN: 1473-5644</identifier><identifier>EISSN: 1473-5644</identifier><identifier>DOI: 10.1099/jmm.0.001751</identifier><language>eng</language><ispartof>Journal of medical microbiology, 2023-01, Vol.72 (9)</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c225t-2763b960249bf0db09971b619635467e787133e444ac6597290b16b10cb2c03a3</cites><orcidid>0000-0003-4964-351X ; 0000-0002-3180-3012 ; 0000-0002-4104-5518 ; 0000-0002-6408-7200 ; 0000-0002-0619-2782 ; 0000-0001-8496-8243 ; 0000-0003-0156-5882</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3733,27901,27902</link.rule.ids></links><search><creatorcontrib>Leitão, Amanda Cavalcante</creatorcontrib><creatorcontrib>Ferreira, Thais Lima</creatorcontrib><creatorcontrib>Gurgel do Amaral Valente Sá, Lívia</creatorcontrib><creatorcontrib>Rodrigues, Daniel Sampaio</creatorcontrib><creatorcontrib>de Souza, Beatriz Oliveira</creatorcontrib><creatorcontrib>Barbosa, Amanda Dias</creatorcontrib><creatorcontrib>Moreira, Lara Elloyse Almeida</creatorcontrib><creatorcontrib>de Andrade Neto, João Batista</creatorcontrib><creatorcontrib>Cabral, Vitória Pessoa de Farias</creatorcontrib><creatorcontrib>Rios, Maria Erivanda França</creatorcontrib><creatorcontrib>Cavalcanti, Bruno Coêlho</creatorcontrib><creatorcontrib>Silva, Jacilene</creatorcontrib><creatorcontrib>Marinho, Emmanuel Silva</creatorcontrib><creatorcontrib>dos Santos, Hélcio Silva</creatorcontrib><creatorcontrib>de Moraes, Manoel Odorico</creatorcontrib><creatorcontrib>Júnior, Hélio Vitoriano Nobre</creatorcontrib><creatorcontrib>da Silva, Cecília Rocha</creatorcontrib><title>Antibacterial activity of menadione alone and in combination with oxacillin against methicillin-resistant Staphylococcus aureus and its impact on biofilms</title><title>Journal of medical microbiology</title><description>Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents. Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress. Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis. Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity. Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml −1 , with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects. Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. 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Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents. Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress. Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis. Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity. Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml −1 , with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects. Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.</abstract><doi>10.1099/jmm.0.001751</doi><orcidid>https://orcid.org/0000-0003-4964-351X</orcidid><orcidid>https://orcid.org/0000-0002-3180-3012</orcidid><orcidid>https://orcid.org/0000-0002-4104-5518</orcidid><orcidid>https://orcid.org/0000-0002-6408-7200</orcidid><orcidid>https://orcid.org/0000-0002-0619-2782</orcidid><orcidid>https://orcid.org/0000-0001-8496-8243</orcidid><orcidid>https://orcid.org/0000-0003-0156-5882</orcidid></addata></record>
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title Antibacterial activity of menadione alone and in combination with oxacillin against methicillin-resistant Staphylococcus aureus and its impact on biofilms
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