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Streptococcus suis is a major pathogen of swine, responsible for a number of chronic and acute infections, and is also emerging as a major zoonotic pathogen, particularly in South-East Asia. Our study of a diverse population of S. suis shows that this organism contains both Type I and Type III phase-variable methyltransferases. In all previous examples, phase-variation of methyltransferases results in genome wide methylation differences, and results in differential regulation of multiple genes, a system known as the phasevarion (phase-variable regulon). We hypothesized that each variant in the Type I and Type III systems encoded a methyltransferase with a unique specificity, and could therefore control a distinct phasevarion, either by recombination-driven shuffling between different specificities (Type I) or by biphasic on-off switching via simple sequence repeats (Type III). Here, we present the identification of the target specificities for each Type III allelic variant from S. suis using single-molecule, real-time methylome analysis. We demonstrate phase-variation is occurring in both Type I and Type III methyltransferases, and show a distinct association between methyltransferase type and presence, and population clades. In addition, we show that the phase-variable Type I methyltransferase was likely acquired at the origin of a highly virulent zoonotic sub-population.

Original publication

DOI

10.1093/nar/gky913

Type

Journal article

Journal

Nucleic acids research

Publication Date

11/2018

Volume

46

Pages

11466 - 11476

Addresses

Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.

Keywords

Animals, Swine, Escherichia coli, Streptococcus suis, Streptococcal Infections, DNA Modification Methylases, Methyltransferases, DNA, Bacterial, Oligonucleotides, DNA Methylation, Epigenesis, Genetic, Gene Expression Regulation, Bacterial, Microsatellite Repeats, Phenotype, Alleles, Genome, Bacterial, Regulon, Genetic Variation