Anti-Quorum Sensing Activities of Gliptins against Pseudomonas aeruginosa and Staphylococcus aureus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strains, Microbiological Media, and Chemicals
2.2. Detection of Minimum Inhibitory Concentrations (MICs) of Gliptins
2.3. Assessment of Gliptins’ Effects on Bacterial Growth
2.4. Evaluation of Antibiofilm Activities of Gliptins
2.5. Visualization of the Biofilm Formation Inhibition
2.6. Quantification of QS- and Virulence-Encoding Gene Expression
2.7. In Vivo Protection Assay
2.8. Ligand Construction, Target Preparation, and Docking Protocol
2.9. Statistical Analysis
3. Results and Discussion
3.1. Determination of Minimum Inhibitory Concentrations (MICs) of Gliptins
3.2. Antibiofilm Activities of Gliptins
3.3. In Vivo Antivirulence Activities of Gliptins
3.4. Gliptins’ Antivirulence Activities Could Be Due to Interference with QS
3.4.1. Gliptins Downregulate QS-Encoding Genes
3.4.2. Multi-Target Docking Analysis on QS Receptors
Docking Simulation on P. aeruginosa Virulence-Regulating Biotargets
Docking Analysis at LasI-Type AHL Synthase Binding Site
Docking Analysis at QscR-Type QS Protein Binding Site
Docking Analysis at LasR-Type Quorum-Sensing Protein Binding Site
Docking Simulation on S. aureus Virulence-Regulating Biotargets
Docking Analysis at ArgC ATP-Binding Domain
Docking Analysis at ArgA Cytoplasmic Response Regulator
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
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Target Gene | Sequence (5′–3′) | Reference |
---|---|---|
lasI | For: CTACAGCCTGCAGAACGACA Rev: ATCTGGGTCTTGGCATTGAG | [16,25,47] |
lasR | For: ACGCTCAAGTGGAAAATTGG Rev: GTAGATGGACGGTTCCCAGA | [16,25,47] |
rhlI | For: CTCTCTGAATCGCTGGAAGG Rev: GACGTCCTTGAGCAGGTAGG | [16,25,47] |
rhlR | For: AGGAATGACGGAGGCTTTTT Rev: CCCGTAGTTCTGCATCTGGT | [16,25,47] |
pqsA | For: TTCTGTTCCGCCTCGATTTC Rev: AGTCGTTCAACGCCAGCAC | [16,25,48] |
pqsR | For: AACCTGGAAATCGACCTGTG Rev: TGAAATCGTCGAGCAGTACG | [16,25,47] |
rpoD | For: GGGCGAAGAAGGAAATGGTC Rev: CAGGTGGCGTAGGTGGAGAAC | [48] |
SigB | For: AAGTGATTCGTAAGGACGTCT Rev: TCGATAACTATAACCAAAGCC T | [49,50] |
SarA | For: TCTTGTTAATGCACAACAACGTAA Rev: TGT TTG CTT CAG TGA TTC GTT T | [51] |
AgrA | For: GGAGTGATTTCAATGGCACA Rev: ATCCAT TTTACTAAGTCACCGATT | [51] |
fnbA | For: AACTGCACAACCAGCAAATG Rev: TTGAGGTTGTGTCGTTTCCTT | [51] |
icaA | For: CAATACTATTTCGGGTGTCTTCACTCT Rev: CAAGAAACTGCAATATCTTCGGTAATCAT | [52] |
16S rRNA | For: TGT CGT GAG ATG TTG GG Rev: CGA TTC CAG CTT CATGT | [50] |
Tested Gliptin | P. aeruginosa | S. aureus |
---|---|---|
Sitagliptin | 10 mg/mL | 5 mg/mL |
Vildagliptin | 10 mg/mL | 5 mg/mL |
Saxagliptin | 2 mg/mL | 1 mg/mL |
Linagliptin | 10 mg/mL | 5 mg/mL |
Gemigliptin | 2 mg/mL | 1 mg/mL |
Anagliptin | 2 mg/mL | 1 mg/mL |
Teneligliptin | 2 mg/mL | 1 mg/mL |
Alogliptin | 2 mg/mL | 1 mg/mL |
Trelagliptin | 2 mg/mL | 1 mg/mL |
Omarigliptin | 2 mg/mL | 1 mg/mL |
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Khayat, M.T.; Abbas, H.A.; Ibrahim, T.S.; Khayyat, A.N.; Alharbi, M.; Darwish, K.M.; Elhady, S.S.; Khafagy, E.-S.; Safo, M.K.; Hegazy, W.A.H. Anti-Quorum Sensing Activities of Gliptins against Pseudomonas aeruginosa and Staphylococcus aureus. Biomedicines 2022, 10, 1169. https://doi.org/10.3390/biomedicines10051169
Khayat MT, Abbas HA, Ibrahim TS, Khayyat AN, Alharbi M, Darwish KM, Elhady SS, Khafagy E-S, Safo MK, Hegazy WAH. Anti-Quorum Sensing Activities of Gliptins against Pseudomonas aeruginosa and Staphylococcus aureus. Biomedicines. 2022; 10(5):1169. https://doi.org/10.3390/biomedicines10051169
Chicago/Turabian StyleKhayat, Maan T., Hisham A. Abbas, Tarek S. Ibrahim, Ahdab N. Khayyat, Majed Alharbi, Khaled M. Darwish, Sameh S. Elhady, El-Sayed Khafagy, Martin K. Safo, and Wael A. H. Hegazy. 2022. "Anti-Quorum Sensing Activities of Gliptins against Pseudomonas aeruginosa and Staphylococcus aureus" Biomedicines 10, no. 5: 1169. https://doi.org/10.3390/biomedicines10051169