Antibiotic activity against intracellular Staphylococcus aureus
(2010)
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- Abstract
- (en) Staphylococcus aureus is a widespread human pathogen, responsible for nosocomial infections and causing diverse diseases including life-threatening ones. Emergence and spread of multidrug resistant S. aureus compel for development of new active molecules. There are nowadays increasing evidences that S. aureus is able to invade and persist into host cells, where bacteria are partially protected from immune response and action of extracellular antibiotics. Using pharmacological models, we wanted to further understand which factors are critical for antibiotic intracellular activity, characterize antistaphylococcal compounds with strong intracellular activity and investigate the predictive value of our in vitro macrophages model of infection through comparison with in vivo studies. Our results showed that acidic medium influences on antibiotic intrinsic activity is a critical factor for intracellular activity towards S. aureus. However, additional parameters, still not elucidated, must play a role in determining intracellular activity. Through activity testing, we showed that quinupristin-dalfopristin, a streptogramin combination, and oritavancin, a newly developped glycopeptide, yield marked intracellular activity regarding to what has already been described in previous studies, including against strains with clinically relevant resistance phenotypes. In the final phase of this study, we assessed activity of plectasin, an antimicrobial peptide currently under development for use in humans, simultaneously in vitro and in vivo. Intracellular activity results obtained in vivo were globally in line with what was observed from in vitro study, therefore suggesting the latter as a relevant screening tool for assessment of antibiotic intracellular activity, although in vivo studies remain essential to achieve a valuable estimation.
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Baudoux, P. (2010). Antibiotic activity against intracellular Staphylococcus aureus. https://hdl.handle.net/2078.5/80733