Use of a Regression Model to Study Host-Genomic Determinants of Phage Susceptibility in MRSA.
Zschach, H., Larsen, M. V., Hasman, H., Westh, H., Nielsen, M., Miedzybrodzki, R., Jonczyk-Matysiak, E., Weber-Dabrowska, B. and Gorski,
Department of Bio and Health Informatics, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark. henrike@bioinformatics.dtu.dk.
GoSeqIt ApS, Ved Klaedebo 9, 2970 Hoersholm, Denmark. MVL@goseqit.com.
Department of Bacteria, Fungi and Parasites, Statens Serum Institut, 2300 Copenhagen S, Denmark. henh@ssi.dk.
Department of Clinical Microbiology, MRSA Knowledge Center, Hvidovre Hospital, 2650 Hvidovre, Denmark. Henrik.torkil.westh@regionh.dk.
Faculty of Health and Medical Sciences, Institute of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark. Henrik.torkil.westh@regionh.dk.
Department of Bio and Health Informatics, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark. mniel@bioinformatics.dtu.dk.
Instituto de Investigaciones Biotecnologicas, Universidad Nacional de San Martin, San Martin, B 1650 HMP, Buenos Aires, Argentina. mniel@bioinformatics.dtu.dk.
Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland. mbrodzki@iitd.pan.wroc.pl.
Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, 02-006 Warsaw, Poland. mbrodzki@iitd.pan.wroc.pl.
Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland. ewa.jonczyk@iitd.pan.wroc.pl.
Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland. weber@iitd.pan.wroc.pl.
Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland. agorski@ikp.pl.
Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, 02-006 Warsaw, Poland. agorski@ikp.pl.
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.
Antibiotics (Basel) 7(1): (2018)