Apr 28, 2020

Systematic Discovery of Salmonella Phage-Host Interactions via High-Throughput Genome-Wide Screens

BioRxiv : the Preprint Server for Biology
B. A. AdlerA. P. Arkin

Abstract

Salmonella species comprise a chronic threat to human health, with over 1.35 million infections and 420 deaths occurring in the US per year due to non-typhoidal, foodborne Salmonella infection. With the rise of antimicrobial resistant (AMR) infections, it is imperative to develop alternative prevention and treatment strategies, such as utilization of lytic bacteriophage as pathogen countermeasures. However, phage-host interactions remain poorly understood, impeding widespread practice. Here, we employed high-throughput, functional analyses to discover the genetic determinants of phage-host interactions between a model enteric Salmonella species, Salmonella enterica serovar Typhimurium (S. typhimurium) and its phages. To rapidly assess genetic contributions to phage sensitivity, we created a 66,996 member randomly barcoded transposon (RB-TnSeq) library in S. typhimurium MS1868. Using this library, we compared fitness across eleven diverse lytic Salmonella phages. Consistent with other loss of function studies against bacteriophage predation, this approach efficiently identified receptors essential to adsorption as well as their regulation. While many of the tested phages bound directly to the lipopolysaccharide (LPS) layer, we r...Continue Reading

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Mentioned in this Paper

Fertility
Gene Polymorphism
Genome-Wide Association Study
Transcription Repressor/Corepressor
Immune System Diseases
Endometrium
Infertility Study
Progesterone
TAP2 gene
Genetic Pleiotropy

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