Distribution of Type I Restriction–Modification Systems in Streptococcus suis: An Outlook

Willemse, Niels; Schultsz, Constance

doi:10.3390/pathogens5040062

Cited by 23 publications

(25 citation statements)

References 30 publications

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“…This not only confirmed the sequence recognized and methylated by ModS2, but also showed that the same allele has the same specificity in different strains of S. suis , and therefore is highly likely to regulate the same phasevarion. The LSS66 methylome demonstrated the presence of two Type I motifs in this strain (Table 3 ), which we predict to be the sequence specificities of the two non-phase-variable Type I loci previously reported to be present in all strains of S. suis ( 37 ), but we cannot confidently assign these signatures to particular methyltransferases without significant additional analysis, which is outside the scope of the current work. An examination of REBASE ( 41 ) shows that these two Type I motifs have not previously been reported.…”

Section: Resultsmentioning

confidence: 74%

“…Our examination of genome sequences of S. suis also demonstrated the presence of two additional Type I R-M loci (YYK_03085-YYK_03100 and YYK_07615-YYK_07625 in strain S735). Previous in depth analysis of Type I R-M systems in S. suis has shown that homologues of these loci are distributed across the majority of S. suis strains ( 37 ). This work also demonstrated the presence of the phase-variable Type I R-M system studied here, but did not show phase-variation within the population of an individual strain as we have.…”

Section: Resultsmentioning

confidence: 99%

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

Atack

Weinert

Tucker

et al. 2018

Nucleic Acids Research

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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.

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Section: Resultsmentioning

confidence: 74%

Section: Resultsmentioning

confidence: 99%

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

Atack

Weinert

Tucker

et al. 2018

Nucleic Acids Research

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“…First of all, a disease-associated marker was described, which is predicted to be a copper-exporting ATPase (SSU207) potentially playing an essential role in copper homeostasis in Gram-positive and -negative bacterial pathogens [ 31 , 32 ]. The second proposed disease-associated marker is annotated as type I restriction-modification (RM) system S protein (SSU1589) in S. suis strain P1/7 (GenBank accession number NC_012925.1) and is supposed to be implicated in the defense of host bacteria [ 33 ]. The third genetic marker is thought to be non-disease-associated and the corresponding protein is suggested to be a putative sugar ATP-binding cassette (ABC) transporter (SSUST30534).…”

Section: Introductionmentioning

confidence: 99%

Population structure, genetic diversity and pathotypes of Streptococcus suis isolated during the last 13 years from diseased pigs in Switzerland

Scherrer

Rosato

Serrano

et al. 2020

Vet Res

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Streptococcus (S.) suis is a globally important swine pathogen, which comprises certain zoonotic serotypes. In this study, a detailed characterization of 88 porcine S. suis isolates was performed by analyzing capsular (cps) types, multilocus sequence typing (MLST) and investigation of the minimum core genome (MCG). In order to focus on the virulence potential of presumable invasive disease-associated S. suis isolates, virulence-associated gene profiles were assessed followed by screening a chosen subset of S. suis strains with a molecular pathotyping tool. Results showed a high genetic variability within this strain collection. In total, seventeen cps types were identified with a predominance of cps type 9 (15.9%) and 6 (14.8%). MLST revealed 48 sequence types (STs) including 41 novel ones. The population structure of S. suis was heterogenous and isolates belonged to eight different clonal complexes (CCs) including CC28 (9.1%), CC1109 (8%), CC13/149 (6.8%), CC1237 (5.7%), CC1 (3.4%), CC17 (3.4%), CC87 (2.3%), and CC1112 (1.1%), whereas a significant portion of isolates (60.2%) could not be assigned to any described CCs. Virulence-associated markers, namely extracellular protein factor (epf), muramidase-released protein (mrp), and suilysin (sly), showed a link with STs rather than with cps types. With this study an expanded knowledge about the population structure and the genetic diversity of S. suis could be achieved, which helps to contribute to an optimal public health surveillance system by promoting a focus on strains with an increased virulence and zoonotic potential.

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“…The findings indicated these two hsdS may each has a unique regulatory mechanism that needs to be elucidated. Additionally, the systematic study of the regulation of virulence in the Type I RM system in SS2 has not previously been performed (Willemse and Schultsz, 2016 ), and that type of systematic study is the goal of this research.…”

Section: Introductionmentioning

confidence: 99%

hsdS, Belonging to the Type I Restriction-Modification System, Contributes to the Streptococcus suis Serotype 2 Survival Ability in Phagocytes

Zhang

et al. 2017

Front. Microbiol.

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Streptococcus suis serotype 2 (SS2) is an important zoonotic agent in swine and humans. Anti-phagocytosis and survival in phagocytic cells and whole blood is essential for bacteria to be pathogenic. In this study, the host specificity determinant specificity subunit (coded by hsdS) of the Type I Restriction-Modification system and two peptidoglycan-binding proteins (coded by lysM and lysM′, respectively), which were simultaneously found to be subjected to transcript-level influence by hsdS, were identified to facilitate the anti-phagocytosis of SS2 to a microglia cell line BV2. Furthermore, they significantly enhanced its survival in BV2, whole blood, and a peroxidation environment (H2O2) (p < 0.05), yet not in the acidic condition based on statistical analysis of the characteristic differences between gene mutants and wild-type SS2. In contrast, another specificity subunit, coded by hsdS′, that belonged to the same Type I Restriction-Modification system, only significantly reduced the survival ability of SS2 in the acidic condition when in the form of a gene-deleted mutant (p < 0.05), but it did not significantly influence the survival ability in other conditions mentioned above or have enhanced anti-phagocytosis action when compared with wild-type SS2. In addition, the mutation of hsdS significantly enhanced the secretion of nitric oxide and TNF-α by BV2 with SS2 incubation (p < 0.05). The SS2 was tested, and it failed to stimulate BV2 to produce IFN-γ. These results demonstrated that hsdS contributed to bacterial anti-phagocytosis and survival in adverse host environments through positively impacting the transcription of two peptidoglycan-binding protein genes, enhancing resistance to reactive oxygen species, and reducing the secretion of TNF-α and nitric oxide by phagocytes. These findings revealed new mechanisms of SS2 pathogenesis.

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Distribution of Type I Restriction–Modification Systems in Streptococcus suis: An Outlook

Cited by 23 publications

References 30 publications

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

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

Population structure, genetic diversity and pathotypes of Streptococcus suis isolated during the last 13 years from diseased pigs in Switzerland

hsdS, Belonging to the Type I Restriction-Modification System, Contributes to the Streptococcus suis Serotype 2 Survival Ability in Phagocytes

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