Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-Lactamase Klebsiella pneumoniae
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Isolates
2.2. Antimicrobial Susceptibility Testing
2.3. DNA Extraction and PCR Amplification
2.4. K. Pneumoniae Survival to Innate Immunity
2.4.1. Susceptibility to Normal Human Serum
2.4.2. Susceptibility to Phagocytosis by Macrophages and Polymorphonuclear Cells
2.5. Synthesis of the PSIR-3 Compound
2.6. Antimicrobial Activity of Photosensitizer Compounds
2.7. Determination of the Synergy between PSIR-3 and Cfx
2.8. Statistical Analyses
3. Results
3.1. Demographic Characterization
3.2. Antibiotic Susceptibility
3.3. Virulence Gene Frequency
3.4. Correlation of Virulence Factors with Antibiotic Resistance
3.5. Association of K2+, ybtS+, and allS+ Virulence Genes to Survive the Innate Immunity
3.6. Susceptibility of Clinical Isolates to aPDI with PSIR-3
3.6.1. Photophysical Properties of the PSIR-3 Compound
3.6.2. Antimicrobial Photodynamic Inhibition of the PSIR-3 over Clinical Isolates
3.6.3. Synergism between aPDI with PSIR-3 and Cefotaxime
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Primers | Gene Type | Amplicon Size |
---|---|---|---|
ybtS | GACGGAAACAGCACGGTAAA | Siderophores | 242 |
GAGCATAATAAGGCGAAAGA | |||
entB | GTCAACTGGGCCTTTGAGCCGTC | Siderophores | 400 |
TATGGGCGTAAACGCCGGTGAT | |||
magA | GGTGCTCTTTACATCATTGC | Capsular serotype K1 and hypermucoviscosity phenotype | 128 |
GCAATGGCCATTTGCGTTAG | |||
rmpA | CATAAGAGTATTGGTTGACAG | Regulator of mucoid phenotype A | 461 |
CTTGCATGAGCCATCTTTCA | |||
K2 | CAACCATGGTGGTCGATTAG | Capsular serotype K2 and hypermucoviscosity phenotype | 531 |
TGGTAGCCATATCCCTTTGG | |||
allS | CATTACGCACCTTTGTCAGC | Allantoin metabolism | 764 |
GAATGTGTCGGCGATCAGCTT | |||
16S | ATTTGAAGAGGTTGCAAACGAT | Gene encoding the 16S ribosomal RNA | 133 |
TTCACTCTGAAGTTTTCTTGTGTTC |
Service | Female | Male | Total | Percent |
---|---|---|---|---|
Outpatient | 12 | 4 | 16 | 13.56% |
surgery | 5 | 5 | 10 | 8.47% |
Endocrinology | 1 | 0 | 1 | 0.85% |
Geriatrics | 1 | 2 | 3 | 2.54% |
Gynecology | 2 | 0 | 2 | 1.69% |
Home hospitalization | 1 | 0 | 1 | 0.85% |
Medicine | 2 | 0 | 24 | 20.34% |
Medical–surgical service | 13 | 11 | 2 | 1.69% |
Pediatrics | 1 | 0 | 1 | 0.85% |
Critical patient unit | 2 | 1 | 3 | 2.54% |
Emergency room | 31 | 10 | 41 | 34.75% |
Urology | 7 | 7 | 14 | 11.86% |
TOTAL | 78 | 40 | 118 | 100% |
Amikacin | Cefotaxime | Ceftazidime | Imipenem | Meropenem | Pip–Taz | |
---|---|---|---|---|---|---|
rmpA | 0.285 | 0.051 | 0.432 | 0.363 | 0.527 | 0.411 |
K2 | 0.158 | 0.002 | 0.919 | 0.102 | 0.588 | 0.001 |
entB | 0.009 | 0.918 | 0.117 | 0.015 | 0.291 | 0.072 |
ybtS | 0.572 | 0.006 | 0.722 | 0.340 | 0.502 | 0.067 |
allS | 0.326 | 0.024 | 0.001 | 0.086 | 0.537 | 0.013 |
Compounds | MIC | MIC Combined | FIC | FIC Index |
---|---|---|---|---|
Cfx | 8.00 | |||
PSIR-3 | 4.00 | 0.17 | 0.02 | 0.15 |
PSIR-3 * | 0.50 | 0.13 | ||
PS-Ru | 8.00 | 6.67 | 0.83 | 1.58 |
PS-Ru * | 6.00 | 0.75 |
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Núñez, C.; Palavecino, A.; González, I.A.; Dreyse, P.; Palavecino, C.E. Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-Lactamase Klebsiella pneumoniae. Pharmaceutics 2021, 13, 603. https://doi.org/10.3390/pharmaceutics13050603
Núñez C, Palavecino A, González IA, Dreyse P, Palavecino CE. Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-Lactamase Klebsiella pneumoniae. Pharmaceutics. 2021; 13(5):603. https://doi.org/10.3390/pharmaceutics13050603
Chicago/Turabian StyleNúñez, Constanza, Annegrett Palavecino, Iván A. González, Paulina Dreyse, and Christian Erick Palavecino. 2021. "Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-Lactamase Klebsiella pneumoniae" Pharmaceutics 13, no. 5: 603. https://doi.org/10.3390/pharmaceutics13050603
APA StyleNúñez, C., Palavecino, A., González, I. A., Dreyse, P., & Palavecino, C. E. (2021). Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-Lactamase Klebsiella pneumoniae. Pharmaceutics, 13(5), 603. https://doi.org/10.3390/pharmaceutics13050603