Abstract
Bacteriophages represent a rich and unique resource of anti-infectives to counter the global problem of antibiotic resis- tance. In this work, we assessed the bactericidal activity of two virulent staphylococcal phages, K and 44AHJD, against S. aureus isolates of clinical significance, and tested their efficacy in vivo. The phage cocktail lysed >85% of the clinical isolates tested. Both the phages were purified by ion-exchange column chromatography following propagation in bioreactors. The purity profiles of the ion-exchange purified phages were compared with those of phages purified using cesium chloride density gradient ultracentrifugation, and infectiousness of the purified phages was confirmed by plaque forming assay. The in vivo efficacy of a phage cocktail was evaluated in an experimental murine nasal colonization model, which showed that the phage cocktail was efficacious. To our knowledge, this is the first report of phage use in an in vivo model of nasal carriage.
Highlights
During the last century, the human pathogen Staphylococcus aureus has become the main cause of nosocomial and community-acquired infections worldwide [1]
In the UK, it is recommended that Methicillin-resistant S. aureus (MRSA) carriers who are receiving prophylaxis for an operation should undergo nasal decolonization with mupirocin, the most commonly used antibiotic for Grampositive bacteria [6]
Because nasal relapses are common within several months [7], and mupirocin resistant S. aureus strains have recently been reported [8], alternate treatments are being pursued by various groups
Summary
The human pathogen Staphylococcus aureus has become the main cause of nosocomial and community-acquired infections worldwide [1]. The effectiveness of bacteriophages for phage therapy against pathogenic bacteria in both animals and humans is well documented [12]. Because they are present in all environments, including water, soil, and air, and are highly specific and lethal to their target host [13], bacteriophages are attractive therapeutic agents for combatting life-threatening bacterial infections in humans and animals. Among 16 studied staphylococcal phages, 44AHJD is highly virulent because of the high translation efficiency of many of its genes [18], making it a good candidate for a therapeutic anti-bacterial agent. Purified phages in the form of a cocktail were evaluated for their in vivo efficacy in an experimental S. aureus nasal colonization mouse model
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