Bioengineered Nisin A Derivatives Display Enhanced Activity against Clinical Neonatal Pathogens
Abstract
:1. Introduction
2. Results
2.1. Bioinformatic and Genomic Analysis
2.2. Screening Nisin Derivatives for Enhanced Antimicrobial Activity
2.3. MIC-Based Investigations of the Specific Activity of Nisin Derivatives
2.4. MIC Investigations of Antibiotics
2.5. Growth Curve Analysis of the Activity of Nisin A and PV Alone and in Combination with Antibiotics
2.6. Kill Curve Analysis of the Activity of Peptide Activity Alone and in Combinations
3. Discussion
4. Materials and Methods
4.1. Bacterial Strains and Growth Conditions
4.2. Whole Genome Sequencing of S. agalactiae Strains
4.3. Bioinformatic Analysis
4.4. Generation and Assessment of a Bank of Nisin Derivatives
4.5. Identification of Nisin Derivatives
4.6. Mass Spectrometry
4.7. Nisin Purification
4.8. Minimum Inhibitory Concentration (MIC) Assay
4.9. Growth/Kill Curves
4.10. 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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Bacterial Strains | Resistant Determinant | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
nsr | nsrFP | msrD | mreA | mefA | mecA | tetM | tetO | ermA | ermB | ermC | IsaC | blaZ | acc6′-aph2″ | fusB | qacA | fosD | |
S. agalactiae | |||||||||||||||||
CIT 67 | + | + | + | + | + | − | + | − | − | − | − | − | − | − | − | − | − |
CIT 85 | + | + | − | + | − | − | + | − | − | + | − | − | − | − | − | − | − |
CIT 87 | + | + | − | + | − | − | + | + | − | + | − | − | − | − | − | − | − |
CIT 239 | + | + | − | + | − | − | − | + | − | + | − | + | − | − | − | − | − |
CIT 364 | + | + | + | + | + | − | + | − | − | − | − | − | − | − | − | − | − |
S. capitis | |||||||||||||||||
AR18 | + | − | − | − | − | + | − | − | − | − | − | − | + | + | + | − | − |
AV80 | + | − | − | − | − | + | − | − | + | − | − | − | + | + | + | − | − |
AY41 | + | − | − | − | − | − | − | − | − | − | − | − | + | − | − | − | − |
BA06 | + | − | − | − | − | + | − | − | − | − | + | − | + | + | − | + | + |
BD01 | + | − | − | − | − | + | − | − | + | − | − | − | + | + | + | − | − |
Strain | MIC (µg/mL) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Nisin | Antibiotics | |||||||||
Nisin A (WT) | PV | T2A-PV | K12A-PV | M17A-PV | Penicillin | Ampicillin | Gentamicin | Erythromycin | Vancomycin | |
L. lactis MG1614 | 0.02 | 0.06 | 0.26 | 0.13 | 0.56 | NT | NT | NT | NT | NT |
L. lactis MG1614 pNP40 | 0.26 | 0.03 * | 0.13 * | 0.06 * | 0.06 * | NT | NT | NT | NT | NT |
S. agalactiae | ||||||||||
CIT67 | 3 | 1.56 * | 6.25 | 3 | 12.5 | 0.04 | 1.56 | 25 | 1 | NT |
CIT 85 | 6 | 12.5 | 25 | 12.5 | NT | 0.012 | 0.097 | 6.25 | 3.13 | NT |
CIT87 | 0.78 | 0.38 * | 3 | 1.56 | NT | 0.02 | 0.78 | 25 | 0.39 | NT |
CIT239 | 12.5 | 6 * | 25 | 25 | NT | 0.02 | 0.097 | 25 | 1.56 | NT |
CIT364 | 1.56 | 0.78 * | 6.25 | 3 | NT | 0.02 | 0.78 | 25 | 0.78 | NT |
S. capitis | ||||||||||
AR18 | 25 | 25 | NT | 50 | NT | >12.5 | >12.5 | >50 | 0.097 | 1.56 |
AV80 | 50 | 50 | NT | 50 | NT | >12.5 | >12.5 | >50 | 12.5 | 3.13 |
AY41 | 25 | 6 * | 12.5 * | 50 | 12.5 | 0.39 | 6.25 | 0.39 | 0.195 | 1.56 |
BA06 | 12.5 | 6 * | NT | 100 | NT | 12.5 | >12.5 | >50 | 12.5 | 1.56 |
BD01 | 25 | 25 | NT | 100 | NT | 6.25 | >12.5 | >50 | 6.25 | 3.13 |
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Desmond, A.; O’Halloran, F.; Cotter, L.; Hill, C.; Field, D. Bioengineered Nisin A Derivatives Display Enhanced Activity against Clinical Neonatal Pathogens. Antibiotics 2022, 11, 1516. https://doi.org/10.3390/antibiotics11111516
Desmond A, O’Halloran F, Cotter L, Hill C, Field D. Bioengineered Nisin A Derivatives Display Enhanced Activity against Clinical Neonatal Pathogens. Antibiotics. 2022; 11(11):1516. https://doi.org/10.3390/antibiotics11111516
Chicago/Turabian StyleDesmond, Anna, Fiona O’Halloran, Lesley Cotter, Colin Hill, and Des Field. 2022. "Bioengineered Nisin A Derivatives Display Enhanced Activity against Clinical Neonatal Pathogens" Antibiotics 11, no. 11: 1516. https://doi.org/10.3390/antibiotics11111516