Menadione as Antibiotic Adjuvant Against <i>P. aeruginosa</i>: Mechanism of Action, Efficacy and Safety
<b>Background/Objectives:</b> Antibiotic resistance in chronic lung infections caused by <i>Pseudomonas aeruginosa</i> requires alternative approaches to improve antibiotic efficacy. One promising approach is the use of adjuvant compounds that complement antibiotic therapy. T...
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MDPI AG
2025-02-01
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| author | Kristela Shehu Marc Schneider Annette Kraegeloh |
| author_facet | Kristela Shehu Marc Schneider Annette Kraegeloh |
| author_sort | Kristela Shehu |
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| description | <b>Background/Objectives:</b> Antibiotic resistance in chronic lung infections caused by <i>Pseudomonas aeruginosa</i> requires alternative approaches to improve antibiotic efficacy. One promising approach is the use of adjuvant compounds that complement antibiotic therapy. This study explores the potential of menadione as an adjuvant to azithromycin against planktonic cells and biofilms of <i>P. aeruginosa</i>, focusing on its mechanisms of action and cytotoxicity in pulmonary cell models. <b>Methods:</b> The effect of menadione in improving the antibacterial and antibiofilm potency of azithromycin was tested against <i>P. aeruginosa</i>. Mechanistic studies in <i>P. aeruginosa</i> and <i>AZMr-E. coli DH5α</i> were performed to probe reactive oxygen species (ROS) production and bacterial membrane disruption. Cytotoxicity of antibacterial concentrations of menadione was assessed by measuring ROS levels and membrane integrity in Calu-3 and A549 lung epithelial cells. <b>Results:</b> Adding 0.5 µg/mL menadione to azithromycin reduced the minimum inhibitory concentration (MIC) by four-fold and the minimum biofilm eradication concentration (MBEC) by two-fold against <i>P. aeruginosa</i>. Adjuvant mechanisms of menadione involved ROS production and disruption of bacterial membranes. Cytotoxicity tests revealed that antibacterial concentrations of menadione (≤64 µg/mL) did not affect ROS levels or membrane integrity in lung cell lines. <b>Conclusions:</b> Menadione enhanced the efficacy of azithromycin against <i>P. aeruginosa</i> while exhibiting a favorable safety profile in lung epithelial cells at antibacterial concentrations. These findings suggest that menadione is a promising antibiotic adjuvant. However, as relevant data on the toxicity of menadione is sparse, further toxicity studies are required to ensure its safe use in complementing antibiotic therapy. |
| format | Article |
| id | doaj-art-64182a883859408c9864d8fa859f0c1d |
| institution | DOAJ |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Antibiotics |
| spelling | doaj-art-64182a883859408c9864d8fa859f0c1d2025-08-20T03:11:19ZengMDPI AGAntibiotics2079-63822025-02-0114216310.3390/antibiotics14020163Menadione as Antibiotic Adjuvant Against <i>P. aeruginosa</i>: Mechanism of Action, Efficacy and SafetyKristela Shehu0Marc Schneider1Annette Kraegeloh2Department of Pharmacy, Biopharmaceutics & Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, GermanyDepartment of Pharmacy, Biopharmaceutics & Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, GermanyINM—Leibniz Institute for New Materials, 66123 Saarbrücken, Germany<b>Background/Objectives:</b> Antibiotic resistance in chronic lung infections caused by <i>Pseudomonas aeruginosa</i> requires alternative approaches to improve antibiotic efficacy. One promising approach is the use of adjuvant compounds that complement antibiotic therapy. This study explores the potential of menadione as an adjuvant to azithromycin against planktonic cells and biofilms of <i>P. aeruginosa</i>, focusing on its mechanisms of action and cytotoxicity in pulmonary cell models. <b>Methods:</b> The effect of menadione in improving the antibacterial and antibiofilm potency of azithromycin was tested against <i>P. aeruginosa</i>. Mechanistic studies in <i>P. aeruginosa</i> and <i>AZMr-E. coli DH5α</i> were performed to probe reactive oxygen species (ROS) production and bacterial membrane disruption. Cytotoxicity of antibacterial concentrations of menadione was assessed by measuring ROS levels and membrane integrity in Calu-3 and A549 lung epithelial cells. <b>Results:</b> Adding 0.5 µg/mL menadione to azithromycin reduced the minimum inhibitory concentration (MIC) by four-fold and the minimum biofilm eradication concentration (MBEC) by two-fold against <i>P. aeruginosa</i>. Adjuvant mechanisms of menadione involved ROS production and disruption of bacterial membranes. Cytotoxicity tests revealed that antibacterial concentrations of menadione (≤64 µg/mL) did not affect ROS levels or membrane integrity in lung cell lines. <b>Conclusions:</b> Menadione enhanced the efficacy of azithromycin against <i>P. aeruginosa</i> while exhibiting a favorable safety profile in lung epithelial cells at antibacterial concentrations. These findings suggest that menadione is a promising antibiotic adjuvant. However, as relevant data on the toxicity of menadione is sparse, further toxicity studies are required to ensure its safe use in complementing antibiotic therapy.https://www.mdpi.com/2079-6382/14/2/163menadioneazithromycin<i>Pseudomonas aeruginosa</i>mechanism of actionlung toxicity |
| spellingShingle | Kristela Shehu Marc Schneider Annette Kraegeloh Menadione as Antibiotic Adjuvant Against <i>P. aeruginosa</i>: Mechanism of Action, Efficacy and Safety Antibiotics menadione azithromycin <i>Pseudomonas aeruginosa</i> mechanism of action lung toxicity |
| title | Menadione as Antibiotic Adjuvant Against <i>P. aeruginosa</i>: Mechanism of Action, Efficacy and Safety |
| title_full | Menadione as Antibiotic Adjuvant Against <i>P. aeruginosa</i>: Mechanism of Action, Efficacy and Safety |
| title_fullStr | Menadione as Antibiotic Adjuvant Against <i>P. aeruginosa</i>: Mechanism of Action, Efficacy and Safety |
| title_full_unstemmed | Menadione as Antibiotic Adjuvant Against <i>P. aeruginosa</i>: Mechanism of Action, Efficacy and Safety |
| title_short | Menadione as Antibiotic Adjuvant Against <i>P. aeruginosa</i>: Mechanism of Action, Efficacy and Safety |
| title_sort | menadione as antibiotic adjuvant against i p aeruginosa i mechanism of action efficacy and safety |
| topic | menadione azithromycin <i>Pseudomonas aeruginosa</i> mechanism of action lung toxicity |
| url | https://www.mdpi.com/2079-6382/14/2/163 |
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