Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against P. aeruginosa Biofilms and Their Effects on the Metabolomic Profile of P. aeruginosa Biofilms
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strains and Growth Conditions
2.2. Antibiotics and Plant-Derived Compounds
2.3. MIC, MBIC, and MBEC Assay
2.4. Evaluation of the Antibiofilm Effects of Ciprofloxacin in Combination with the Compounds on Mono- and Triple-Species Biofilms of P. aeruginosa PAO1 and SEM Analysis
2.5. Alterations in Virulence Characteristics of P. aeruginosa Biofilm Cells
2.5.1. Swarming
2.5.2. Twitching
2.5.3. Quantification of Pyocyanin
2.6. Expression of the QS-Related Genes in Biofilms
2.7. Metabolomic Analysis
2.8. Statistical Analysis
3. Results
3.1. Effect of the Compounds and Ciprofloxacin on the Planktonic and Biofilm Cells of P. aeruginosa
3.2. Comparison of the Effect of Compound–Ciprofloxacin Combinations with Sub-MBIC Values on Mono- and Triple-Species Biofilms of P. aeruginosa
3.3. Influence of the Compounds and Ciprofloxacin Combinations on Virulence Properties of P. aeruginosa
3.4. The Impact of Ciprofloxacin Combined with the Compounds on QS Gene Expressions of P. aeruginosa Biofilm Cells
3.5. Effect of Ciprofloxacin and Compounds Combinations on the Metabolic Profile of P. aeruginosa Biofilm Cells
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Agents | MICs (mg/L) | MBICs (mg/L) | MBECs (mg/L) | ||
---|---|---|---|---|---|
Alone * | Alone ** | Combinations *** (CIP + Compounds) | Alone ** | Combinations *** (CIP + Compounds) | |
Ciprofloxacin | 0.039 | 0.06 | - | 0.13 | - |
Curcumin | 0.25 | 0.82 | 0.001 + 0.008 | >0.82 | 0.13 + 2 |
Azathioprine | 0.25 | 0.82 | 0.008 + 0.06 | >0.82 | 0.13 + 2 |
Resveratrol | 0.25 | 0.2 | 0.03 + 0.25 | >0.82 | 0.13 + 2 |
Catechin hydrate | 0.51 | 0.82 | 0.03 + 0.26 | >0.82 | >0.13 + 2 |
Baicalein | 0.13 | 0.2 | 0.001 + 0.008 | >0.82 | 0.13 + 2 |
l-canavanine | 0.1 | 0.82 | 0.004 + 0.03 | >0.82 | 0.13 + 2 |
4-nitropyridine N-oxide | 0.02 | 0.41 | 0.008 + 0.06 | >0.82 | 0.13 + 2 |
p-benzoquinone | 0.06 | 0.41 | 0.008 + 0.06 | >0.82 | 0.13 + 2 |
Esculetin hydrate | 0.51 | 0.82 | 0.002 + 0.02 | >0.82 | 0.13 + 2 |
Cinnamaldehyde | 0.26 | 0.41 | 0.002 + 0.02 | >0.82 | 0.13 + 2 |
Curc. | Cinnam. | Curc. | Cinnam. | ||||
---|---|---|---|---|---|---|---|
Carbohydrate | Citric acid | 0.44↓ | - | Nitrogen | Pyroglutamic acid | 0.13↓ | 1.7↑ |
Lactose | 0.32↓ | - | Aspartic acid | 0.03↓ | 2.08↑ | ||
Glucose | 4.04↑ | - | Glutamic acid | 0.06↓ | - | ||
Melibiose | 0.1↓ | 1.83↑ | N-acetyl-l-glutamic acid | 0.3↓ | - | ||
Mannose | 1.78↑ | - | |||||
Maltotriose | 0.02↓ | 2.92↑ | Lipid | Glyceric acid | 0.25↓ | - | |
Maltotriitol | 0.01↓ | 2.61↑ | Glycine | 0.4↓ | - | ||
Melezitose | 0.01↓ | 2.3↑ | Glycerol-phosphate | 0.35↓ | - | ||
Glucuronic acid | 0.24↓ | - | Beta-glycerolphosphate | 0.42↓ | - | ||
Amino Acid | Threonine | 0.43↓ | - | ||||
Glyceraldehyde | 1.83↑ | - | |||||
Proline | 0.24↓ | - | 3-phosphoglycerate | 0.04↓ | - | ||
Methionine | 0.28↓ | - | |||||
Lysine | 0.01↓ | 0.12↓ | Nucleotid | Uracil | 0.13↓ | 0.17↓ | |
Phenylalanine | 0.49↓ | - | Uridine 5’-monophosphate | 1.5↑ | 0.02↓ | ||
Tryptophane | 0.19↓ | Ribulose-5-phosphate | 0.23↓ | 0.06↓ | |||
Amines | Phenylethylamine | 0.03↓ | 0.43↓ | ||||
Pyrophosphate | 6.58↑ | - | |||||
2-amino-1-phenylethanol | 0.01↓ | 0.42↓ | Cytidine-5’-monophosphate | 0.35↓ | - | ||
Tyramine | 0.14↓ | - | Porphine | 3.19↑ | - |
Esculetin hyd | Baicalein hyd | ||
---|---|---|---|
Carbohydrate | Fumaric acid | - | 1.61↑ |
Malic acid | - | 1.64↑ | |
Melibiose | 1.51↑ | 1.71↑ | |
Mannose | 1.47↑ | 1.83↑ | |
Maltotriose | 2.08↑ | - | |
Maltotriitol | 1.75↑ | - | |
Melezitose | 1.56↑ | - | |
Glucose-6-phosphate | - | 3.15↑ | |
Amino Acid | Aspartic Acid | 2.8↑ | - |
Lysine | 4.13↑ | - | |
Tryptophane | 1.87↑ | 2.89↑ | |
Nitrogen | Pyroglutamic Acid | 1.65↑ | - |
Glutamic acid | 2.37↑ | - | |
Amines | Phenylethylamine | 3.52↑ | 4.39↑ |
2-amino-1-phenylethanol | 12.83↑ | 1.47↑ | |
Tyramine | 1.68↑ | 2.51↑ | |
Lipid | Glycerol-phosphate | - | 1.79↑ |
Beta-glycerolphosphate | - | 1.65↑ | |
Nucleotid | Uracil | 6.11↑ | 11.01↑ |
Uridine 5’-monophosphate | 0.41↓ | 3.81↑ | |
Ribulose-5-phosphate | 1.38↑ | 9.27↑ | |
Pyrophosphate | 1.49↑ | 5.89↑ |
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Kart, D.; Reçber, T.; Nemutlu, E.; Sagiroglu, M. Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against P. aeruginosa Biofilms and Their Effects on the Metabolomic Profile of P. aeruginosa Biofilms. Antibiotics 2021, 10, 414. https://doi.org/10.3390/antibiotics10040414
Kart D, Reçber T, Nemutlu E, Sagiroglu M. Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against P. aeruginosa Biofilms and Their Effects on the Metabolomic Profile of P. aeruginosa Biofilms. Antibiotics. 2021; 10(4):414. https://doi.org/10.3390/antibiotics10040414
Chicago/Turabian StyleKart, Didem, Tuba Reçber, Emirhan Nemutlu, and Meral Sagiroglu. 2021. "Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against P. aeruginosa Biofilms and Their Effects on the Metabolomic Profile of P. aeruginosa Biofilms" Antibiotics 10, no. 4: 414. https://doi.org/10.3390/antibiotics10040414