Aspartic acid unveils as antibiofilm agent and tobramycin adjuvant against mucoid and small colony variants of Pseudomonas aeruginosa isolates in vitro within cystic fibrosis airway mucus

Antibiotics are central to managing airway infections in cystic fibrosis (CF), yet current treatments often fail due to the presence of Pseudomonas aeruginosa biofilms, settling down the need for seeking therapies targeting biofilms. This study aimed to investigate the antibiofilm activity of aspart...

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Main Authors: Rosana Monteiro, Ana Margarida Sousa, Maria Olívia Pereira
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Biofilm
Online Access:http://www.sciencedirect.com/science/article/pii/S2590207524000777
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author Rosana Monteiro
Ana Margarida Sousa
Maria Olívia Pereira
author_facet Rosana Monteiro
Ana Margarida Sousa
Maria Olívia Pereira
author_sort Rosana Monteiro
collection DOAJ
description Antibiotics are central to managing airway infections in cystic fibrosis (CF), yet current treatments often fail due to the presence of Pseudomonas aeruginosa biofilms, settling down the need for seeking therapies targeting biofilms. This study aimed to investigate the antibiofilm activity of aspartic acid and its potential as an adjuvant to tobramycin against P. aeruginosa biofilms formed by mucoid and small colony variant (SCV) tobramycin tolerant strain. We assessed the effect of aspartic acid on both surface-attached and suspended P. aeruginosa biofilms within CF artificial mucus and investigated the synergistic impact of combining it with non-lethal tobramycin concentrations. Our findings showed that aspartic acid inhibited planktonic P. aeruginosa without affecting its viability and prevented biofilm formation by hindering bacterial adhesion or interfering with EPS production, depending on the experimental conditions. In CF mucus, aspartic acid significantly reduced bacterial growth, with the highest inhibition observed when combined with tobramycin, showing notable effects against the mucoid and tolerant SCV strain. Despite these reductions, P. aeruginosa repopulated the mucus within 24 h of stress withdrawal. Additional strategies, including delayed tobramycin application and a second dose of co-application of aspartic acid and tobramycin were explored to address bacterial survival and recovery. Although none of the strategies eradicated P. aeruginosa, the second co-application resulted in slower bacterial recovery rates.In conclusion, this study highlighted aspartic acid as an effective antibiofilm agent and demonstrated for the first time its potential as an adjuvant to tobramycin. The combined use of aspartic acid and tobramycin offers a promising advancement in CF therapeutics, particularly against P. aeruginosa biofilms formed by mucoid and SCV strains, mitigating their antibiotic resistance.
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spelling doaj-art-aa9363c457b04700a3e132122cd3df872025-01-07T04:17:30ZengElsevierBiofilm2590-20752025-06-019100252Aspartic acid unveils as antibiofilm agent and tobramycin adjuvant against mucoid and small colony variants of Pseudomonas aeruginosa isolates in vitro within cystic fibrosis airway mucusRosana Monteiro0Ana Margarida Sousa1Maria Olívia Pereira2CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, PortugalCEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal; LABBELS – Associate Laboratory, Braga/Guimarães, PortugalCEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal; LABBELS – Associate Laboratory, Braga/Guimarães, Portugal; Corresponding author. CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.Antibiotics are central to managing airway infections in cystic fibrosis (CF), yet current treatments often fail due to the presence of Pseudomonas aeruginosa biofilms, settling down the need for seeking therapies targeting biofilms. This study aimed to investigate the antibiofilm activity of aspartic acid and its potential as an adjuvant to tobramycin against P. aeruginosa biofilms formed by mucoid and small colony variant (SCV) tobramycin tolerant strain. We assessed the effect of aspartic acid on both surface-attached and suspended P. aeruginosa biofilms within CF artificial mucus and investigated the synergistic impact of combining it with non-lethal tobramycin concentrations. Our findings showed that aspartic acid inhibited planktonic P. aeruginosa without affecting its viability and prevented biofilm formation by hindering bacterial adhesion or interfering with EPS production, depending on the experimental conditions. In CF mucus, aspartic acid significantly reduced bacterial growth, with the highest inhibition observed when combined with tobramycin, showing notable effects against the mucoid and tolerant SCV strain. Despite these reductions, P. aeruginosa repopulated the mucus within 24 h of stress withdrawal. Additional strategies, including delayed tobramycin application and a second dose of co-application of aspartic acid and tobramycin were explored to address bacterial survival and recovery. Although none of the strategies eradicated P. aeruginosa, the second co-application resulted in slower bacterial recovery rates.In conclusion, this study highlighted aspartic acid as an effective antibiofilm agent and demonstrated for the first time its potential as an adjuvant to tobramycin. The combined use of aspartic acid and tobramycin offers a promising advancement in CF therapeutics, particularly against P. aeruginosa biofilms formed by mucoid and SCV strains, mitigating their antibiotic resistance.http://www.sciencedirect.com/science/article/pii/S2590207524000777
spellingShingle Rosana Monteiro
Ana Margarida Sousa
Maria Olívia Pereira
Aspartic acid unveils as antibiofilm agent and tobramycin adjuvant against mucoid and small colony variants of Pseudomonas aeruginosa isolates in vitro within cystic fibrosis airway mucus
Biofilm
title Aspartic acid unveils as antibiofilm agent and tobramycin adjuvant against mucoid and small colony variants of Pseudomonas aeruginosa isolates in vitro within cystic fibrosis airway mucus
title_full Aspartic acid unveils as antibiofilm agent and tobramycin adjuvant against mucoid and small colony variants of Pseudomonas aeruginosa isolates in vitro within cystic fibrosis airway mucus
title_fullStr Aspartic acid unveils as antibiofilm agent and tobramycin adjuvant against mucoid and small colony variants of Pseudomonas aeruginosa isolates in vitro within cystic fibrosis airway mucus
title_full_unstemmed Aspartic acid unveils as antibiofilm agent and tobramycin adjuvant against mucoid and small colony variants of Pseudomonas aeruginosa isolates in vitro within cystic fibrosis airway mucus
title_short Aspartic acid unveils as antibiofilm agent and tobramycin adjuvant against mucoid and small colony variants of Pseudomonas aeruginosa isolates in vitro within cystic fibrosis airway mucus
title_sort aspartic acid unveils as antibiofilm agent and tobramycin adjuvant against mucoid and small colony variants of pseudomonas aeruginosa isolates in vitro within cystic fibrosis airway mucus
url http://www.sciencedirect.com/science/article/pii/S2590207524000777
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