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Bactericidal Effect of Tomatidine-Tobramycin Combination against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Is Enhanced by Interspecific Small-Molecule Interactions.

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Boulanger, Simon; Mitchell, Gabriel; Bouarab, Kamal; Marsault, Éric; Cantin, André; Frost, Éric; Déziel, Éric ORCID logoORCID: https://orcid.org/0000-0002-4609-0115 et Malouin, François (2015). Bactericidal Effect of Tomatidine-Tobramycin Combination against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Is Enhanced by Interspecific Small-Molecule Interactions. Antimicrobial Agents and Chemotherapy , vol. 59 , nº 12. pp. 7458-64. DOI: 10.1128/AAC.01711-15.

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Résumé

This study investigated the antibacterial activity of the plant alkaloid tomatidine (TO) against Staphylococcus aureus grown in presence of Pseudomonas aeruginosa. Since the P. aeruginosa exoproduct 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) is known to cause respiratory deficiency in S. aureus and that respiratory-deficient S. aureus are known to be hypersensitive to TO, we performed kill kinetics of TO (8 mug/ml) against S. aureus in co-culture with P. aeruginosa. Kill kinetics were also carried out using P. aeruginosa mutants deficient in the production of different exoproducts and quorum sensing-related compounds. After 24h in co-culture, TO increased the killing of S. aureus by 3.4 log10 CFU/ml in comparison to that observed in a co-culture without TO. The effect of TO was abolished when S. aureus was in co-culture with the lasR-/rhlR-, pqsA-, pqsL- or lasA- mutant of P. aeruginosa. The bactericidal effect of TO against S. aureus in co-culture with the pqsL- mutant was restored by supplemental HQNO. In a S. aureus mono-culture, 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 co-culture with P. aeruginosa and addition of tobramycin significantly suppressed the growth of both microorganisms. TO shows a strong bactericidal effect against S. aureus when co-cultured with P. aeruginosa. The combination of TO and tobramycin may represent a new treatment approach for cystic fibrosis patients frequently co-colonized by MRSA and P. aeruginosa.

Type de document: Article
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 05 janv. 2016 22:21
Dernière modification: 21 févr. 2022 19:57
URI: https://espace.inrs.ca/id/eprint/3156

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