Apr 27, 2020

Joint antibiotic and phage therapy: addressing the limitations of a seemingly ideal phage for treating Staphylococcus aureus infections

BioRxiv : the Preprint Server for Biology
B. BerryhillBruce R Levin

Abstract

In response to increasing frequencies of antibiotic resistant pathogens, there has been a resurrection of interest in the use of bacteriophage to treat bacterial infections: phage therapy. Here we explore the potential of a seemingly ideal phage, PYOSa, for combination phage and antibiotic treatment of Staphylococcus aureus infections. (i) This K like phage has a broad host range; all 83 clinical isolates of S. aureus tested were susceptible to PYOSa. (ii) Because the mode of action of PYOSa S. aureus is unlikely to generate surface mutants resistant to PYOSa; none were observed in the 13 clinical isolates tested. (iii) PYOSa kills S. aureus at high rates. On the downside, the results of our experiments and tests of the joint action of PYOSa and antibiotics raise issues that must be addressed before PYOSa is employed clinically. Despite the maintenance of the phage, due to the ascent of potentially pathogenic small colony variants, PYOSa does not clear populations of S. aureus; following an initial demise the bacterial populations return to densities similar to that of phage-free controls. Bacteriostatic antibiotics prevent PYOSa from replicating on S. aureus and bactericidal antibiotics are antagonistic to the action of PYOSa....Continue Reading

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Mentioned in this Paper

Body Regions
Midline (Qualifier Value)
Magnetic Resonance Imaging
Genes
CNTNAP2
Epilepsy
CNTNAP2 protein, human
Brain
Gene Mutation
Neurodevelopmental Disorders

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