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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Use of a Regression Model to Study Host-Genomic Determinants of Phage Susceptibility in MRSA

Research output: Contribution to journalJournal articleResearchpeer-review

  • Henrike Zschach
  • Mette V Larsen
  • Henrik Hasman
  • Henrik Westh
  • Morten Nielsen
  • Ryszard Międzybrodzki
  • Ewa Jończyk-Matysiak
  • Beata Weber-Dąbrowska
  • Andrzej Górski
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Staphylococcus aureus is a major agent of nosocomial infections. Especially in methicillin-resistant strains, conventional treatment options are limited and expensive, which has fueled a growing interest in phage therapy approaches. We have tested the susceptibility of 207 clinical S. aureus strains to 12 (nine monovalent) different therapeutic phage preparations and subsequently employed linear regression models to estimate the influence of individual host gene families on resistance to phages. Specifically, we used a two-step regression model setup with a preselection step based on gene family enrichment. We show that our models are robust and capture the data's underlying signal by comparing their performance to that of models build on randomized data. In doing so, we have identified 167 gene families that govern phage resistance in our strain set and performed functional analysis on them. This revealed genes of possible prophage or mobile genetic element origin, along with genes involved in restriction-modification and transcription regulators, though the majority were genes of unknown function. This study is a step in the direction of understanding the intricate host-phage relationship in this important pathogen with the outlook to targeted phage therapy applications.

Original languageEnglish
JournalAntibiotics
Volume7
Issue number1
ISSN2079-6382
DOIs
Publication statusPublished - 1 Feb 2018

    Research areas

  • Journal Article

ID: 52644893