Microbiological and molecular assessment of bacteriophage ISP for the control of Staphylococcus aureus

Katrien Vandersteegen, Wesley Mattheus, Pieter Jan Ceyssens, Florence Bilocq, Daniel de Vos, Jean Paul Pirnay, Jean Paul Noben, Maia Merabishvili, Urszula Lipinska, Katleen Hermans, Rob Lavigne

Research output: Contribution to journalArticlepeer-review

Abstract

The increasing antibiotic resistance in bacterial populations requires alternatives for classical treatment of infectious diseases and therefore drives the renewed interest in phage therapy. Methicillin resistant Staphylococcus aureus (MRSA) is a major problem in health care settings and live-stock breeding across the world. This research aims at a thorough microbiological, genomic, and proteomic characterization of S. aureus phage ISP, required for therapeutic applications. Host range screening of a large batch of S. aureus isolates and subsequent fingerprint and DNA microarray analysis of the isolates revealed a substantial activity of ISP against 86% of the isolates, including relevant MRSA strains. From a phage therapy perspective, the infection parameters and the frequency of bacterial mutations conferring ISP resistance were determined. Further, ISP was proven to be stable in relevant in vivo conditions and subcutaneous as well as nasal and oral ISP administration to rabbits appeared to cause no adverse effects. ISP encodes 215 gene products on its 138,339 bp genome, 22 of which were confirmed as structural proteins using tandem electrospray ionization-mass spectrometry (ESI-MS/MS), and shares strong sequence homology with the 'Twort-like viruses'. No toxic or virulence-associated proteins were observed. The microbiological and molecular characterization of ISP supports its application in a phage cocktail for therapeutic purposes.

Original languageEnglish
Article numbere24418
JournalPLoS ONE
Volume6
Issue number9
DOIs
Publication statusPublished - 9 Sept 2011

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