Streptococcus suis contains multiple phase-variable methyltransferases that show a discrete lineage distribution

• Published in: Nucleic acids research 2018-11, Vol.46 (21), p.11466-11476
• Main Authors: Atack, John M, Weinert, Lucy A, Tucker, Alexander W, Husna, Asma U, Wileman, Thomas M, F. Hadjirin, Nazreen, Hoa, Ngo T, Parkhill, Julian, Maskell, Duncan J, Blackall, Patrick J, Jennings, Michael P
• Format: Article
• Language: English
• Subjects: Alleles; Animals; DNA Methylation; DNA Modification Methylases - metabolism; DNA, Bacterial - metabolism; Epigenesis, Genetic; Escherichia coli; Gene Expression Regulation, Bacterial; Genetic Variation; Genome, Bacterial; Methyltransferases - genetics; Microsatellite Repeats; Nucleic Acid Enzymes; Oligonucleotides - genetics; Phenotype; Regulon; Streptococcal Infections - microbiology; Streptococcal Infections - veterinary; Streptococcus suis - enzymology; Streptococcus suis - genetics; Swine
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gky913

Abstract 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.