Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against <i>P. aeruginosa</i> Biofilms and Their Effects on the Metabolomic Profile of <i>P. aeruginosa</i> Biofilms
Introduction: Alternative anti-biofilm agents are needed to combat <i>Pseudomonas aeruginosa</i> infections. The mechanisms behind these new agents also need to be revealed at a molecular level. Materials and methods: The anti-biofilm effects of 10 plant-derived compounds on <i>P....
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MDPI AG
2021-04-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/4/414 |
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| author | Didem Kart Tuba Reçber Emirhan Nemutlu Meral Sagiroglu |
| author_facet | Didem Kart Tuba Reçber Emirhan Nemutlu Meral Sagiroglu |
| author_sort | Didem Kart |
| collection | DOAJ |
| description | Introduction: Alternative anti-biofilm agents are needed to combat <i>Pseudomonas aeruginosa</i> infections. The mechanisms behind these new agents also need to be revealed at a molecular level. Materials and methods: The anti-biofilm effects of 10 plant-derived compounds on <i>P. aeruginosa</i> biofilms were investigated using minimum biofilm eradication concentration (MBEC) and virulence assays. The effects of ciprofloxacin and compound combinations on <i>P. aeruginosa</i> in mono and triple biofilms were compared. A metabolomic approach and qRT-PCR were applied to the biofilms treated with ciprofloxacin in combination with baicalein, esculin hydrate, curcumin, and cinnamaldehyde at sub-minimal biofilm inhibitory concentration (MBIC) concentrations to highlight the specific metabolic shifts between the biofilms and to determine the quorum sensing gene expressions, respectively. Results: The combinations of ciprofloxacin with curcumin, baicalein, esculetin, and cinnamaldehyde showed more reduced MBICs than ciprofloxacin alone. The quorum sensing genes were downregulated in the presence of curcumin and cinnamaldehyde, while upregulated in the presence of baicalein and esculin hydrate rather than for ciprofloxacin alone. The combinations exhibited different killing effects on <i>P. aeruginosa</i> in mono and triple biofilms without affecting its virulence. The findings of the decreased metabolite levels related to pyrimidine and lipopolysaccharide synthesis and to down-regulated alginate and <i>lasI</i> expressions strongly indicate the role of multifactorial mechanisms for curcumin-mediated <i>P. aeruginosa</i> growth inhibition. Conclusions: The use of curcumin, baicalein, esculetin, and cinnamaldehyde with ciprofloxacin will help fight against <i>P. aeruginosa</i> biofilms. To the best of our knowledge, this is the first study of its kind to define the effect of plant-based compounds as possible anti-biofilm agents with low MBICs for the treatment of <i>P. aeruginosa</i> biofilms through metabolomic pathways. |
| first_indexed | 2024-03-10T12:27:57Z |
| format | Article |
| id | doaj.art-5fe4507380ac476e922a30123bb25585 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T12:27:57Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-5fe4507380ac476e922a30123bb255852023-11-21T14:55:01ZengMDPI AGAntibiotics2079-63822021-04-0110441410.3390/antibiotics10040414Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against <i>P. aeruginosa</i> Biofilms and Their Effects on the Metabolomic Profile of <i>P. aeruginosa</i> BiofilmsDidem Kart0Tuba Reçber1Emirhan Nemutlu2Meral Sagiroglu3Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Hacettepe University, Ankara 06100, TurkeyDepartment of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, TurkeyDepartment of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, TurkeyDepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, Hacettepe University, Ankara 06100, TurkeyIntroduction: Alternative anti-biofilm agents are needed to combat <i>Pseudomonas aeruginosa</i> infections. The mechanisms behind these new agents also need to be revealed at a molecular level. Materials and methods: The anti-biofilm effects of 10 plant-derived compounds on <i>P. aeruginosa</i> biofilms were investigated using minimum biofilm eradication concentration (MBEC) and virulence assays. The effects of ciprofloxacin and compound combinations on <i>P. aeruginosa</i> in mono and triple biofilms were compared. A metabolomic approach and qRT-PCR were applied to the biofilms treated with ciprofloxacin in combination with baicalein, esculin hydrate, curcumin, and cinnamaldehyde at sub-minimal biofilm inhibitory concentration (MBIC) concentrations to highlight the specific metabolic shifts between the biofilms and to determine the quorum sensing gene expressions, respectively. Results: The combinations of ciprofloxacin with curcumin, baicalein, esculetin, and cinnamaldehyde showed more reduced MBICs than ciprofloxacin alone. The quorum sensing genes were downregulated in the presence of curcumin and cinnamaldehyde, while upregulated in the presence of baicalein and esculin hydrate rather than for ciprofloxacin alone. The combinations exhibited different killing effects on <i>P. aeruginosa</i> in mono and triple biofilms without affecting its virulence. The findings of the decreased metabolite levels related to pyrimidine and lipopolysaccharide synthesis and to down-regulated alginate and <i>lasI</i> expressions strongly indicate the role of multifactorial mechanisms for curcumin-mediated <i>P. aeruginosa</i> growth inhibition. Conclusions: The use of curcumin, baicalein, esculetin, and cinnamaldehyde with ciprofloxacin will help fight against <i>P. aeruginosa</i> biofilms. To the best of our knowledge, this is the first study of its kind to define the effect of plant-based compounds as possible anti-biofilm agents with low MBICs for the treatment of <i>P. aeruginosa</i> biofilms through metabolomic pathways.https://www.mdpi.com/2079-6382/10/4/414<i>P. aeruginosa</i>plant-derived compoundsmetabolomicMBICbiofilm |
| spellingShingle | Didem Kart Tuba Reçber Emirhan Nemutlu Meral Sagiroglu Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against <i>P. aeruginosa</i> Biofilms and Their Effects on the Metabolomic Profile of <i>P. aeruginosa</i> Biofilms Antibiotics <i>P. aeruginosa</i> plant-derived compounds metabolomic MBIC biofilm |
| title | Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against <i>P. aeruginosa</i> Biofilms and Their Effects on the Metabolomic Profile of <i>P. aeruginosa</i> Biofilms |
| title_full | Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against <i>P. aeruginosa</i> Biofilms and Their Effects on the Metabolomic Profile of <i>P. aeruginosa</i> Biofilms |
| title_fullStr | Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against <i>P. aeruginosa</i> Biofilms and Their Effects on the Metabolomic Profile of <i>P. aeruginosa</i> Biofilms |
| title_full_unstemmed | Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against <i>P. aeruginosa</i> Biofilms and Their Effects on the Metabolomic Profile of <i>P. aeruginosa</i> Biofilms |
| title_short | Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against <i>P. aeruginosa</i> Biofilms and Their Effects on the Metabolomic Profile of <i>P. aeruginosa</i> Biofilms |
| title_sort | sub inhibitory concentrations of ciprofloxacin alone and combinations with plant derived compounds against i p aeruginosa i biofilms and their effects on the metabolomic profile of i p aeruginosa i biofilms |
| topic | <i>P. aeruginosa</i> plant-derived compounds metabolomic MBIC biofilm |
| url | https://www.mdpi.com/2079-6382/10/4/414 |
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