Core defense hotspots within Pseudomonas aeruginosa are a consistent and rich source of anti-phage defense systems

Author:

Johnson Matthew C1ORCID,Laderman Eric1,Huiting Erin1,Zhang Chi2,Davidson Alan2ORCID,Bondy-Denomy Joseph134

Affiliation:

1. Department of Microbiology and Immunology, University of California , San Francisco, San Francisco , CA 94158, USA

2. Departments of Biochemistry and Molecular Genetics, University of Toronto, 661 University Ave , Toronto , ON M5G 1M1 , Canada

3. Quantitative Biosciences Institute, University of California , San Francisco, San Francisco , CA 94158, USA

4. Innovative Genomics Institute , Berkeley , CA 94720, USA

Abstract

Abstract Bacteria use a diverse arsenal of anti-phage immune systems, including CRISPR-Cas and restriction enzymes. Recent advances in anti-phage system discovery and annotation tools have unearthed many unique systems, often encoded in horizontally transferred defense islands, which can be horizontally transferred. Here, we developed Hidden Markov Models (HMMs) for defense systems and queried microbial genomes on the NCBI database. Out of the 30 species with >200 completely sequenced genomes, our analysis found Pseudomonas aeruginosa exhibits the greatest diversity of anti-phage systems, as measured by Shannon entropy. Using network analysis to identify the common neighbors of anti-phage systems, we identified two core defense hotspot loci (cDHS1 and cDHS2). cDHS1 is up to 224 kb (median: 26 kb) with varied arrangements of more than 30 distinct immune systems across isolates, while cDHS2 has 24 distinct systems (median: 6 kb). Both cDHS regions are occupied in a majority of P. aeruginosa isolates. Most cDHS genes are of unknown function potentially representing new anti-phage systems, which we validated by identifying a novel anti-phage system (Shango) commonly encoded in cDHS1. Identifying core genes flanking immune islands could simplify immune system discovery and may represent popular landing spots for diverse MGEs carrying anti-phage systems.

Funder

National Institutes of Health

Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation

CIHR

Felix Biotechnology

Publisher

Oxford University Press (OUP)

Subject

Genetics

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