Phage Therapy against Staphylococcus aureus: Selection and Optimization of Production Protocols of Novel Broad-Spectrum Silviavirus Phages
Phage therapy a promising antimicrobial strategy to address antimicrobial
resistance for infections caused by the major human pathogen Staphylococcus aureus. Development
of therapeutic phages for human use should follow pharmaceutical standards, including selection
of strictly lytic bacteriophages with high therapeutic potential and optimization of their production
Here, we describe three novel Silviavirus phages active against 82% of a large
collection of strains (n = 150) representative of various methicillin-susceptible and -resistant S. aureus
clones circulating worldwide. We also investigated the optimization of the efficiency and safety of
phage amplification protocols. To do so, we selected a well-characterized bacterial strain in order
to (i) maximize phage production yields, reaching phage titres of 1011 PFU/mL in only 4 h; and
(ii) facilitate phage purity while minimizing the risk of the presence of contaminants originating
from the bacterial host; i.e., secreted virulence factors or induced temperate phages.
In sum, we propose a quality-by-design approach for the amplification of broad-spectrum anti-S.
aureus phages, facilitating the subsequent steps of the manufacturing process; namely, purification
and quality control.