Combinatory Effect of Nitroxoline and Gentamicin in the Control of Uropathogenic Enterococci Infections
Abstract
:1. Introduction
2. Results
2.1. Susceptibility Profile of E. faecalis Strains for GEN and NTX
2.2. Synergism Testing of Selected Concentrations of Nitroxoline and Gentamicin on Uropathogenic E. faecalis Strains Using the Checkerboard Assay
- Synergistic (FICi ≤ 0.5);
- Additive (0.5 > FICi ≤ 1.0);
- Indifferent (1.0 > FICi ≤ 4);
- Antagonistic (FICi > 4).
2.3. Testing Inhibition of Biofilm Formation at Selected Concentrations of Nitroxoline and Gentamicin
2.4. The Effect of the NTX/GEN Combined Treatment on the Morphology of ATCC29212 Strain Cells
2.5. MALDI-TOF MS Analysis of ATCC29212 Wild and Mutant Strains
3. Discussion
4. Materials and Methods
4.1. Strains, Culture Conditions, and Chemicals
4.2. Determination of Minimum Inhibitory Concentrations of Selected Uropathogenic Enterococci
4.3. Biofilm Formation Assay
4.4. Examination of the Interaction of Selected Concentrations of Nitroxoline and Gentamicin on E. faecalis Strains Using the Checkerboard Assay
4.5. Examination of the Bacterial Cell Morphology Using Transmission Electron Microscopy (TEM)
4.6. Examination of the Protein Profile of Selected Uropathogenic Enterococci Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS)
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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E. faecalis Strain | Gentamicin | Nitroxoline | GROUP | ||
---|---|---|---|---|---|
MIC (µg/mL) | MIC (µg/mL) | MBC (µg/mL) | MAC (µg/mL) | ||
E46 | 2 | 8 | 32 | 4 | 1 |
E61 | 4 | 16 | >64 | 8 | 2 |
E34 | 8 | 2 | 32 | 2 | 3 |
E36 | 8 | 4 | 32 | 2 | |
ATCC29212 | 8 | 8 | 32 | 4 | 4 |
E69 | 8 | 8 | >64 | 4 | |
E89 | 16 | 4 | 32 | 2 | 5 |
E85 | 16 | 4 | 32 | 2 | |
E10 | 16 | 4 | 32 | 2 | |
E16 | 16 | 8 | >64 | 4 | 6 |
E35 | 16 | 8 | >64 | 4 | |
E47 | 128 | 4 | 32 | 2 | 7 |
E15 | 128 | 4 | 32 | 2 | |
E32 | 128 | 4 | 32 | 2 | |
E84 | 128 | 4 | 32 | 2 | |
E95 | 128 | 4 | 32 | 2 | |
E79 | 128 | 8 | 32 | 4 | 8 |
E38 | 128 | 8 | 32 | 4 | |
E55 | 128 | 8 | 32 | 4 | |
E45 | 128 | 8 | 32 | 4 | |
E72 | 128 | 8 | 32 | 4 | |
E41 | 128 | 8 | 32 | 4 | |
E39 | 512 | 4 | 32 | 2 | 9 |
E8 | 512 | 4 | 32 | 2 | |
E58 | 512 | 4 | 32 | 2 | |
E1 | 512 | 4 | 32 | 2 | |
E7 | 512 | 8 | 32 | 4 | 10 |
E48 | 512 | 8 | 32 | 4 | |
E37 | 512 | 8 | >64 | 4 |
Synergistic Antimicrobial Effect | ||||
---|---|---|---|---|
E. faecalis Strains | Individual MICs NTX/GEN (μg/mL) | Combination MICs NTX+GEN (μg/mL) | ||
GROUP 8 (E79, E38, E55, E45, E72, E41) | 8/128 | 2/8 | 2/16 | 2/32 |
GROUP 4 (ATCC29212, E69) | 8/8 | 2/0.5 | 2/1 | 2/2 |
Additive Antimicrobial Effect | |||||||
---|---|---|---|---|---|---|---|
E. faecalis Strains | Individual MICs NTX/GEN (μg/mL) | Combination MICs NTX + GEN (μg/mL) | |||||
GROUP 8 (E79, E38, E55, E45, E72, E41) | 8/128 | 4/8 | 4/16 | 4/32 | 4/64 | 2/64 | 1/64 |
GROUP 4 (ATCC29212, E69) | 8/8 | 4/0.5 | 4/1 | 4/2 | 4/4 | 2/4 | |
GROUP 7 (E47, E15, E32, E84, E95) | 4/128 | 2/8 | 2/16 | 2/32 | 2/64 | 1/64 | |
GROUP 3 (E34, E36) | 4/8 | 2/0.5 | 2/1 | 2/2 | 2/4 | 1/4 | |
GROUP 5 (E89, E85, E10) | 4/16 | 2/2 | 2/4 | 2/8 | 1/8 | ||
GROUP 2 (E61) | 8/4 | 4/0.5 | 4/1 | 4/2 | |||
GROUP 6 (E16, E35) | 8/16 | 4/2 | 4/4 | 4/8 | |||
GROUP 9 (E39, E8, E58, E1) | 4/512 | 2/8 | 2/16 | 2/32 | 2/64 | 2/128 | 2/256 |
GROUP 10 (E7, E48, E37) | 8/512 | 4/8 | 4/16 | 4/32 | 4/64 | 4/128 | 4/256 |
GROUP 1 (E46) | 8/2 | 4/0.5 | 4/1 | 2/1 |
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Repac Antić, D.; Kovač, B.; Kolenc, M.; Brčić Karačonji, I.; Gobin, I.; Petković Didović, M. Combinatory Effect of Nitroxoline and Gentamicin in the Control of Uropathogenic Enterococci Infections. Antibiotics 2024, 13, 829. https://doi.org/10.3390/antibiotics13090829
Repac Antić D, Kovač B, Kolenc M, Brčić Karačonji I, Gobin I, Petković Didović M. Combinatory Effect of Nitroxoline and Gentamicin in the Control of Uropathogenic Enterococci Infections. Antibiotics. 2024; 13(9):829. https://doi.org/10.3390/antibiotics13090829
Chicago/Turabian StyleRepac Antić, Davorka, Bruno Kovač, Marko Kolenc, Irena Brčić Karačonji, Ivana Gobin, and Mirna Petković Didović. 2024. "Combinatory Effect of Nitroxoline and Gentamicin in the Control of Uropathogenic Enterococci Infections" Antibiotics 13, no. 9: 829. https://doi.org/10.3390/antibiotics13090829