These Are the Genes You're Looking For: Finding Host Resistance Genes. Issue 4 (April 2021)

• Record Type: Journal Article
• Authors: Bourgeois, Jeffrey S.; Smith, Clare M.; Ko, Dennis C.
• Is Part Of: Trends in microbiology. Volume 29:Issue 4(2021)
• Page Start: 346
• Page End: 362
• Publication Date: 2021-04
• Subjects: genetic resistance -- bacteria -- eQTL -- GWAS -- dual RNA-seq -- collaborative cross; Microbiology -- Periodicals; Infection -- Periodicals; Virulence (Microbiology) -- Periodicals; Infection -- Periodicals; Microbiology -- Periodicals; Virulence -- Periodicals; Microbiologie -- Périodiques; Infection -- Périodiques; Virulence (Microbiologie) -- Périodiques; Infection; Microbiology; Virulence (Microbiology); 579
• DOI: 10.1016/j.tim.2020.09.006
• Languages: English
• ISSNs: 0966-842X

Abstract

Abstract : Humanity's ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host–pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics contributes to host resistance or susceptibility to bacterial infection. Here we discuss current trends in defining host–bacterial interactions at the genome-wide level, including screens that harness CRISPR/Cas9 genome editing, natural genetic variation, proteomics, and transcriptomics. We report on the merits, limitations, and findings of these innovative screens and discuss their complementary nature. Finally, we speculate on future innovation as we continue to progress through the postgenomic era and towards deeper mechanistic insight and clinical applications. Highlights: Understanding host–microbe interactions remains critical as growing antibiotic resistance, new outbreaks, and re-emerging pathogens put lives at risk. Microbiologists and infectious disease researchers have leveraged and advanced the genomic technological breakthroughs of the last decade. Advances in clustered regularly interspaced short palindromic repeats (CRISPR/Cas9)-mediated genome editing and reduced sequencing costs have made CRISPR screens the dominant loss-of-function and gain-of-function screening platform. Advances in sequencing, high-throughput technologies, and resources for model organisms and humans have dramatically improved natural diversity screens. Such resources include consortia with repositories for electronic medical records and human cell lines, and model-organism diversity panels. Integrating pathogen diversity into host resistance screens helps to further define the genetic landscape of host–pathogen interactions.