Modification and Synergistic Studies of a Novel Frog Antimicrobial Peptide against Pseudomonas aeruginosa Biofilms
Abstract
:1. Introduction
2. Results
2.1. ‘Shotgun’ Cloning of Peptide Nigrosin-6VL Biosynthetic Precursor Complementary DNA (cDNA)
2.2. Predicted Secondary Structure and Physicochemical Characteristics of the Original Peptide Nigrosin-6VL
2.3. Physicochemical Properties and Structural Modification of Nigrosin-6VL
2.4. Anti-Planktonic Microorganism Activity Selection of Nigrosin-6VL and Its Analogues
2.5. Haemolysis Activity and TI Values of Nigrosin-6VL and Its Analogues
2.6. Time-Killing Kinetic Studies of Nigrosin-6VL and 2170-2R
2.7. Antimicrobial Mechanism Studies of Nigrosin-6VL and 2170-2R
2.7.1. Effects on Bacterial Outer Membrane Permeability
2.7.2. Effects of Nigrosin-6VL and 2170-2R on Bacterial Intracellular Membrane Permeability
2.8. Peptide and Antibiotic Co-Administration Studies
2.9. Anti-Biofilm Studies
2.10. Peptide and Antibiotic Co-Administration Studies of Anti-Biofilm Activities
3. Discussion
4. Materials and Methods
4.1. Acquisition of Skin Secretions from Odorrana andersonii
4.2. Molecular Cloning
4.3. Peptide Sequence Analysis, Secondary Structural Prediction, and Verification
4.4. Synthesis and Purification of Peptides
4.5. Anti-Planktonic Microorganism Activity Study
4.6. Haemolysis Assay and TI Value Calculation
4.7. Time-Killing Kinetic Assay
4.8. The SYTOX Green of the Bacterial Membrane Permeabilisation Assay
4.9. Outer Membrane Assay
4.10. Anti-Biofilm Assay
4.11. Peptide and Antibiotic Co-Administration Study
4.11.1. Peptide and Antibiotic Co-Administration of MIC Assay
4.11.2. Peptide and Antibiotic Co-Administration of MBIC Assay
4.12. Method of Measurement and Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Peptide | Sequence | Calculated Molecular Mass | Charge |
---|---|---|---|
Nigrosin-6VL | GLLSGVLGAGKKIVCGLSGRC | 1986.088 | +3 |
1885-C | GLLSGVLGAGKKIV-GLSGRC | 1885.099 | +3 |
1885-R | GLLSGVLGAGKKIVCGLSGR- | 1885.547 | +3 |
1924-A | GLLSGVLGAGKKIVAGLSGRA | 1924.037 | +3 |
1782-R | GLLSGVLGAGKKIV-GLSGR- | 1782.097 | +3 |
2057-C | GLLRGVLGAGKKIVCGLSGRC | 2057.665 | +4 |
2085-R | GLLRAVLAAGKKIVCGLSGRC | 2084.890 | +4 |
2170-2R | GLLRAVLRAGKKIVCGLSGRC | 2169.932 | +5 |
Strains (Codes) | MICs/MBCs (µM) | |||||||
---|---|---|---|---|---|---|---|---|
Nigrosin-6VL | 1782-R | 1885-C | 1924-A | 1885-R | 2057-C | 2085-R | 2170-2R | |
S. aureus (ATCC 6538) | 16/32 | >128/>128 | >128/>128 | 128/>128 | 128/>128 | 128/>128 | 16/16 | 4/8 |
MRSA (NCTC 12493) | >128/>128 | >128/>128 | >128/>128 | >128/>128 | 64/64 | 64/128 | 16/32 | 16/16 |
E. faecalis (NCTC 12697) | >128/>128 | >128/>128 | >128/>128 | >128/>128 | >128/>128 | >128/>128 | 64/256 | 128/128 |
E. coli (ATCC 8739) | 64/128 | 128/>128 | 16/32 | 64/128 | 32/64 | 16/32 | 16/16 | 4/8 |
K. pneumoniae (ATCC 43816) | 128/128 | >128/>128 | 64/128 | 64/128 | 32/64 | 64/128 | 32/64 | 32/32 |
P. aeruginosa (ATCC CRM 9027) | 32/128 | >128/>128 | 64/128 | 128/>128 | 32/64 | 64/128 | 64/64 | 32/32 |
A. baumannii (BAA 747) | >128/>128 | >128/>128 | >128/>128 | >128/>128 | 128/>128 | >128/>128 | 32/64 | 4/8 |
C. albicans (ATCC 10231) | 128/>128 | >128/>128 | >128/>128 | 64/128 | >128/>128 | >128/>128 | 32/32 | 64/128 |
Peptide | HC10 (μM) | GM (μM) | TI Value * | ||||
---|---|---|---|---|---|---|---|
G+ Bacteria | G− Bacteria | Yeast | G+ Bacteria | G− Bacteria | Yeast | ||
Nigrosin-6VL | >256 | 101.59 | 90.51 | 128.00 | 5.04 | 5.66 | 4.00 |
1782-R | >256 | 256.00 | 215.27 | 256.00 | 2.00 | 2.38 | 2.00 |
1885-C | >256 | 256.00 | 64.00 | 256.00 | 2.00 | 8.00 | 2.00 |
1924-A | >256 | 203.19 | 107.63 | 64.00 | 2.52 | 4.76 | 8.00 |
1885-R | >256 | 128.00 | 45.25 | 256.00 | 4.00 | 11.31 | 2.00 |
2057-C | >256 | 128.00 | 64.00 | 256.00 | 4.00 | 8.00 | 2.00 |
2085-R | >256 | 25.40 | 32.00 | 32.00 | 20.16 | 16.00 | 16.00 |
2170-2R | >256 | 25.16 | 11.31 | 64.00 | 20.35 | 45.27 | 8.00 |
Strains | MICs/MBCs (µM) | |||
---|---|---|---|---|
Levofloxacin | Cefepime | Gentamicin | Vancomycin | |
S. aureus ATCC 6538 | 0.5/0.5 | 32/64 | 2/2 | 8/64 |
MRSA NCTC 12493 | 0.25/0.5 | 16/32 | 1/2 | 4/8 |
E. faecalis NCTC 12697 | 2/8 | 128/>128 | 16/32 | 32/>128 |
E. coli ATCC 8739 | 0.25/0.5 | 8/16 | 2/4 | 32/>128 |
K. pneumoniae ATCC 43816 | >128/>128 | 128/>128 | 1/1 | >128/>128 |
P. aeruginosa ATCC CRM 9027 | 2/2 | 2/2 | 0.25/0.5 | >128/>128 |
A. baumannii BAA 747 | 1/1 | 1/2 | >128/>128 | >128/>128 |
Strains | FICI Values | |||||||
---|---|---|---|---|---|---|---|---|
Vancomycin | Cefepime | Levofloxacin | Gentamicin | |||||
Nigrosin-6VL | 2170-2R | Nigrosin-6VL | 2170-2R | Nigrosin-6VL | 2170-2R | Nigrosin-6VL | 2170-2R | |
S. aureus ATCC 6538 | 2.25 | 0.625 | 0.625 | 1 | 0.625 | 0.625 | 1.5 | 1 |
MRSA NCTC 12493 | 1 | 0.625 | 0.75 | 0.75 | 2 | 1.125 | 0.5 | 0.375 |
E. faecalis NCTC 12697 | 0.625 | 0.625 | 0.125 | 0.15625 | 0.625 | 0.625 | 0.625 | 0.625 |
E. coli ATCC 8739 | 1.125 | >4 | 0.375 | 0.53125 | 0.375 | 0.375 | 0.125 | 0.125 |
K. pneumoniae ATCC 43816 | 1.125 | 1.125 | 0.1875 | 0.1875 | 0.625 | 1 | 0.1875 | 0.15625 |
P. aeruginosa ATCC CRM 9027 | >4 | 1.125 | 0.5 | 0.5 | 0.5 | 0.625 | 0.5 | 0.5 |
A. baumannii BAA 747 | 1.25 | 0.625 | 1 | 1.5 | >4 | >4 | 0.1875 | 0.25 |
Strains | MBICs/MBECs (µM) | |
---|---|---|
Nigrosin-6VL | 2170-2R | |
S. aureus ATCC 6538 | 128/>128 | 4/16 |
MRSA NCTC 12493 | >128/>128 | 4/16 |
E. faecalis NCTC 12697 | >128/>128 | 32/>128 |
K. pneumoniae ATCC 43816 | >128/>128 | 32/>128 |
P. aeruginosa ATCC CRM 9027 | >128/>128 | >128/>128 |
A. baumannii BAA 747 | >128/>128 | 8/16 |
Strains | MBICs/MBECs (µM) | |
---|---|---|
Cefepime | Gentamicin | |
S. aureus ATCC 6538 | 4/8 | 8/16 |
MRSA NCTC 12493 | >128/>128 | 2/>128 |
E. faecalis NCTC 12697 | >128/>128 | >128/>128 |
K. pneumoniae ATCC 43816 | >128/>128 | 32/32 |
P. aeruginosa ATCC CRM 9027 | >128/>128 | 2/4 |
A. baumannii BAA 747 | 128/>128 | 8/16 |
Strains | Biofilm FICI Values | |||
---|---|---|---|---|
Cefepime | Gentamicin | |||
Nigrosin-6VL | 2170-2R | Nigrosin-6VL | 2170-2R | |
S. aureus ATCC 6538 | 1 | 1 | 0.5 | 0.25 |
MRSA NCTC 12493 | 0.75 | 0.5 | 0.375 | 1.125 |
E. faecalis NCTC 12697 | 0.5 | 0.375 | 0.5 | 0.6125 |
K. pneumoniae ATCC 43816 | 1.25 | 3 | 0.5 | 1.125 |
P. aeruginosa ATCC CRM 9027 | 0.3125 | 0.5 | 0.5 | 1 |
A. baumannii BAA 747 | 0.5 | 0.625 | 0.5 | 0.75 |
Strains | MBICs/MBECs (µM) | |||
---|---|---|---|---|
Cefepime | Gentamicin | Nigrosin-6VL | 2170-2R | |
P. aeruginosa ATCC CRM 9027 | >128/>128 | 2/4 | >128/>128 | >128/>128 |
P. aeruginosa ATCC 27853 | 2/4 | 4/>128 | >128/>128 | 8/16 |
P. aeruginosa ATCC BAA-2108 | 64/>128 | 16/128 | >128/>128 | >128/>128 |
P. aeruginosa 01 | 4/>128 | 4/8 | >128/>128 | 32/64 |
P. aeruginosa 14 | 8/>128 | 2/4 | >128/>128 | >128/>128 |
Strains | Biofilm FICI Values | |||
---|---|---|---|---|
Cefepime | Gentamicin | |||
Nigrosin-6VL | 2170-2R | Nigrosin-6VL | 2170-2R | |
P. aeruginosa ATCC CRM 9027 | 0.3125 | 0.5 | 0.5 | 1 |
P. aeruginosa ATCC 27853 | 1 | 0.5 | 0.25 | 0.25 |
P. aeruginosa ATCC BAA-2108 | 0.625 | 1 | 1 | >3 |
P. aeruginosa 01 | 0.625 | 0.5 | 0.625 | 1 |
P. aeruginosa 14 | 0.25 | 0.375 | 0.5 | 1 |
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Liu, X.; Shi, D.; Cheng, S.; Chen, X.; Ma, C.; Jiang, Y.; Wang, T.; Chen, T.; Shaw, C.; Wang, L.; et al. Modification and Synergistic Studies of a Novel Frog Antimicrobial Peptide against Pseudomonas aeruginosa Biofilms. Antibiotics 2024, 13, 574. https://doi.org/10.3390/antibiotics13070574
Liu X, Shi D, Cheng S, Chen X, Ma C, Jiang Y, Wang T, Chen T, Shaw C, Wang L, et al. Modification and Synergistic Studies of a Novel Frog Antimicrobial Peptide against Pseudomonas aeruginosa Biofilms. Antibiotics. 2024; 13(7):574. https://doi.org/10.3390/antibiotics13070574
Chicago/Turabian StyleLiu, Xinze, Daning Shi, Shiya Cheng, Xiaoling Chen, Chengbang Ma, Yangyang Jiang, Tao Wang, Tianbao Chen, Chris Shaw, Lei Wang, and et al. 2024. "Modification and Synergistic Studies of a Novel Frog Antimicrobial Peptide against Pseudomonas aeruginosa Biofilms" Antibiotics 13, no. 7: 574. https://doi.org/10.3390/antibiotics13070574