Bactericidal Effect of Tomatidine-Tobramycin Combination against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Is Enhanced by Interspecific Small-Molecule Interactions
| Autor: | François Malouin, Kamal Bouarab, Gabriel Mitchell, André M. Cantin, Eric Marsault, Eric Frost, Eric Déziel, Simon Boulanger |
|---|---|
| Přispěvatelé: | Centre d'Étude et de Valorisation de la Diversité Microbienne . Département de biologie (CEVDM), Université de Sherbrooke (UdeS), Département de pharmacologie, Département de médecine, Département de microbiologie et d′infectiologie, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), This study was supported by grants from Cystic Fibrosis Canada to F.M., A.C., and E.H.F., as well as to F.M. and E.M., and by a team grant from the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT) to F.M., K.B., and E.M. E.D. was supported by Canadian Institutes of Health Research (CIHR) operating grant MOP-97888 and holds a Canada Research Chair |
| Rok vydání: | 2015 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Virulence Factors [SDV]Life Sciences [q-bio] Mutant Microbial Sensitivity Tests Biology medicine.disease_cause Microbiology Tomatine chemistry.chemical_compound Bacterial Proteins Tobramycin medicine Pharmacology (medical) Mechanisms of Action: Physiological Effects Pharmacology Pseudomonas aeruginosa Quorum Sensing Drug Synergism [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Methicillin-resistant Staphylococcus aureus Coculture Techniques Anti-Bacterial Agents 3. Good health Quorum sensing Infectious Diseases chemistry Staphylococcus aureus Mutation Hydroxyquinolines Metalloproteases Trans-Activators Antibacterial activity medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2015, 59 (12), pp.7458-64. ⟨10.1128/aac.01711-15⟩ |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.01711-15 |
| Popis: | This study investigated the antibacterial activity of the plant alkaloid tomatidine (TO) against Staphylococcus aureus grown in the presence of Pseudomonas aeruginosa . Since the P. aeruginosa exoproduct 4-hydroxy-2-heptylquinoline- N -oxide (HQNO) is known to cause a respiratory deficiency in S. aureus and respiratory-deficient S. aureus are known to be hypersensitive to TO, we assessed kill kinetics of TO (8 μg/ml) against S. aureus in coculture with P. aeruginosa . Kill kinetics were also assessed using P. aeruginosa mutants deficient in the production of different exoproducts and quorum sensing-related compounds. After 24 h in coculture, TO increased the killing of S. aureus by 3.4 log 10 CFU/ml in comparison to that observed in a coculture without TO. The effect of TO was abolished when S. aureus was in coculture with the lasR rhlR , pqsA , pqsL , or lasA mutant of P. aeruginosa . The bactericidal effect of TO against S. aureus in coculture with the pqsL mutant was restored by supplemental HQNO. In an S. aureus monoculture, the combination of HQNO and TO was bacteriostatic, indicating that the pqsL mutant produced an additional factor required for the bactericidal effect. The bactericidal activity of TO was also observed against a tobramycin-resistant methicillin-resistant S. aureus (MRSA) in coculture with P. aeruginosa , and the addition of tobramycin significantly suppressed the growth of both microorganisms. TO shows a strong bactericidal effect against S. aureus when cocultured with P. aeruginosa . The combination of TO and tobramycin may represent a new treatment approach for cystic fibrosis patients frequently cocolonized by MRSA and P. aeruginosa . |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|