Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics
Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence, biofilm formation and antibiotic efflux pump expression. The development of effective small molecules targeting the QS system and biofilm formation represents a novel attractive strategy. In this present study, the effects of a se...
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| Format: | Article |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.611009/full |
| _version_ | 1818461384322580480 |
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| author | Dejing Shang Dejing Shang Xue Han Wanying Du Zhiru Kou Fengquan Jiang |
| author_facet | Dejing Shang Dejing Shang Xue Han Wanying Du Zhiru Kou Fengquan Jiang |
| author_sort | Dejing Shang |
| collection | DOAJ |
| description | Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence, biofilm formation and antibiotic efflux pump expression. The development of effective small molecules targeting the QS system and biofilm formation represents a novel attractive strategy. In this present study, the effects of a series of Trp-containing peptides on the QS-regulated virulence and biofilm development of multidrug-resistant P. aeruginosa, as well as their synergistic antibacterial activity with three classes of traditional chemical antibiotics were investigated. The results showed that Trp-containing peptides at low concentrations reduced the production of QS-regulated virulence factors by downregulating the gene expression of both the las and rhl systems in the strain MRPA0108. Biofilm formation was inhibited in a concentration-dependent manner, which was associated with extracellular polysaccharide production inhibition by downregulating pelA, algD, and pslA transcription. These changes correlated with alterations in the extracellular production of pseudomonal virulence factors and swarming motility. In addition, the combination of Trp-containing peptides at low concentration with the antibiotics ceftazidime and piperacillin provided synergistic effects. Notably, L11W and L12W showed the highest synergy with ceftazidime and piperacillin. A mechanistic study demonstrated that the Trp-containing peptides, especially L12W, significantly decreased β-lactamase activity and expression of efflux pump genes OprM, MexX, and MexA, resulting in a reduction in antibiotic efflux from MRPA0108 cells and thus increasing the antibacterial activity of these antibiotics against MRPA0108. |
| first_indexed | 2024-12-14T23:45:17Z |
| format | Article |
| id | doaj.art-24258d6cd2b6449f9351abf877a4ac9d |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-14T23:45:17Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-24258d6cd2b6449f9351abf877a4ac9d2022-12-21T22:43:24ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-02-011210.3389/fmicb.2021.611009611009Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With AntibioticsDejing Shang0Dejing Shang1Xue Han2Wanying Du3Zhiru Kou4Fengquan Jiang5School of Life Sciences, Liaoning Normal University, Dalian, ChinaLiaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, ChinaSchool of Life Sciences, Liaoning Normal University, Dalian, ChinaSchool of Life Sciences, Liaoning Normal University, Dalian, ChinaSchool of Life Sciences, Liaoning Normal University, Dalian, ChinaClinical Laboratory Department of the First Affiliated Hospital, Dalian Medical University, Dalian, ChinaPseudomonas aeruginosa uses quorum sensing (QS) to control virulence, biofilm formation and antibiotic efflux pump expression. The development of effective small molecules targeting the QS system and biofilm formation represents a novel attractive strategy. In this present study, the effects of a series of Trp-containing peptides on the QS-regulated virulence and biofilm development of multidrug-resistant P. aeruginosa, as well as their synergistic antibacterial activity with three classes of traditional chemical antibiotics were investigated. The results showed that Trp-containing peptides at low concentrations reduced the production of QS-regulated virulence factors by downregulating the gene expression of both the las and rhl systems in the strain MRPA0108. Biofilm formation was inhibited in a concentration-dependent manner, which was associated with extracellular polysaccharide production inhibition by downregulating pelA, algD, and pslA transcription. These changes correlated with alterations in the extracellular production of pseudomonal virulence factors and swarming motility. In addition, the combination of Trp-containing peptides at low concentration with the antibiotics ceftazidime and piperacillin provided synergistic effects. Notably, L11W and L12W showed the highest synergy with ceftazidime and piperacillin. A mechanistic study demonstrated that the Trp-containing peptides, especially L12W, significantly decreased β-lactamase activity and expression of efflux pump genes OprM, MexX, and MexA, resulting in a reduction in antibiotic efflux from MRPA0108 cells and thus increasing the antibacterial activity of these antibiotics against MRPA0108.https://www.frontiersin.org/articles/10.3389/fmicb.2021.611009/fullmultidrug-resistant Pseudomonas aeruginosaTrp-containing peptidequorum sensingvirulence factorbiofilmsynergy |
| spellingShingle | Dejing Shang Dejing Shang Xue Han Wanying Du Zhiru Kou Fengquan Jiang Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics Frontiers in Microbiology multidrug-resistant Pseudomonas aeruginosa Trp-containing peptide quorum sensing virulence factor biofilm synergy |
| title | Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics |
| title_full | Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics |
| title_fullStr | Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics |
| title_full_unstemmed | Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics |
| title_short | Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics |
| title_sort | trp containing antibacterial peptides impair quorum sensing and biofilm development in multidrug resistant pseudomonas aeruginosa and exhibit synergistic effects with antibiotics |
| topic | multidrug-resistant Pseudomonas aeruginosa Trp-containing peptide quorum sensing virulence factor biofilm synergy |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.611009/full |
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