[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Evaluation of the activity of a combination of three bacteriophages alone or in association with antibiotics on Staphylococcus aureus embedded in biofilm or internalised in osteoblasts
Camille Kolenda, Jérôme Josse, Mathieu Medina, Cindy Fevre, Sébastien Lustig, Tristan Ferry, Frédéric Laurent
Staphylococcus aureus is responsible for difficult-to-treat bone and joint infections (BJIs). This is related to its ability to form biofilm, and to be internalised and persist inside osteoblasts. Recently, bacteriophage therapy has emerged as a promising option to improve treatment of such infections but data on its activity against the specific bacterial lifestyles presented above remain scarce.
We evaluated the activity of a combination of three bacteriophages, recently used for compassionate treatment in France, against S. aureus HG001 in a model of staphylococcal biofilm and a model of osteoblasts infection, alone or in association with vancomycin or rifampicin.
The activity of bacteriophages against biofilm-embedded S. aureus was dose-dependent. In addition, synergistic effects were observed when bacteriophages were combined with antibiotics used at the lowest concentrations. Phage penetration into osteoblasts was observed only when the cells were infected, suggesting a S. aureus-dependent Trojan horse mechanism for internalisation. The intracellular bacterial count of bacteria in infected osteoblasts treated with bacteriophages, as well as with vancomycin, was significantly higher than in cells treated with lysostaphin, used as control condition, owing to the absence of intracellular activity, and the rapid killing of bacteria released after death of infected cells. These results suggest that bacteriophages are both inactive in the intracellular compartment after being internalised in infected osteoblasts, and present a delayed killing effect on bacteria released after cell lysis into the extracellular compartment which avoid to prevent them from infecting other osteoblasts.
The combination of bacteriophages tested was highly active against S. aureus embedded in biofilm but showed no activity against intracellular bacteria in the cell model used.
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Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; Bacteriophages.