Characterization of the Type I Restriction Modification System Broadly Conserved among Group A Streptococci

DebRoy, Sruti; Shropshire, William C; Tran, Chau Nguyen; Hao, Haiping; Gohel, Marc; Galloway-Peña, Jessica; Hanson, Blake; Shelburne, Samuel A.

doi:10.1128/msphere.00799-21

Cited by 22 publications

(23 citation statements)

References 72 publications

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“…An additional non-synonymous SNP leading to the premature STOP codon was present in the type I restriction endonuclease gene hsdM (SP5448_08275) within the 5448Δ slo genetic backgrounds ( Table S2 ). hsd mutations have previously been shown to alter Strep A transformability, yet do not alter broad transcriptional changes ( 30 , 31 ).…”

Section: Resultsmentioning

confidence: 99%

“…The type 1 restriction-modification system has a role in DNA methylation. Investigations by others on the role of this system in gene expression and virulence determined that the type I restriction-modification system has an effect in protection against exogenous DNA ( 30 ), and that mutations (spontaneous or introduced) to hsdM within this system can be exploited to increase transformability in a strain, with no obvious change in growth or off-target gene expression ( 31 ). The outcomes of these studies suggest that the hsdM mutation in 5448Δ slo was positively selected for during the transformation process and this mutation was then maintained in the passaged derivative 5448Δ slo covS1 .…”

Section: Discussionmentioning

confidence: 99%

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Streptolysin O Deficiency in Streptococcus pyogenes M1T1 covR/S Mutant Strain Attenuates Virulence in In Vitro and In Vivo Infection Models

Langshaw

Reynolds

Ozberk

et al. 2023

mBio

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Streptolysin O Deficiency in Streptococcus pyogenes M1T1 covR/S Mutant Strain Attenuates Virulence in In Vitro and In Vivo Infection Models

Langshaw

Reynolds

Ozberk

et al. 2023

mBio

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“…In particular, Streptococcus pneumoniae has a conserved phase-variable Type I R-M system with multiple hsdS alleles that can affect nutrient acquisition, stress tolerance, and virulence (40, 44). In contrast, a single- hsdS Type I R-M system deletion mutant in Streptococcus pyogenes doesn’t have altered transcription (45), suggesting a regulatory role is not a universal characteristic of Type I R-M systems. However, DNA methylation is poorly studied among plant pathogenic bacteria and limited examples of methylation affecting gene expression exist.…”

Section: Discussionmentioning

confidence: 99%

Natural recombination among Type I restriction-modification systems creates diverse genomic methylation patterns among Xylella fastidiosa strains

O'Leary

Burbank

2022

Preprint

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Xylella fastidiosa is an important bacterial pathogen of plants causing high consequence diseases in agricultural crops around the world. Although as a species X. fastidiosa can infect an extremely broad range of host plants, significant variability exists between strains and subspecies groups in virulence on specific host plant species, and other traits such as growth habits. Natural competence and horizontal gene transfer are believed to occur frequently in X. fastidiosa, and likely influences the evolution of this pathogen. However, some X. fastidiosa strains are extremely difficult or impossible to manipulate genetically using standard transformation techniques. Several restriction-modification systems are encoded in the X. fastidiosa genome, including multiple Type I R-M systems that may influence horizontal gene transfer and recombination. In this study, several conserved Type I R-M systems were compared across 129 X. fastidiosa genome assemblies representing all known subspecies and 32 sequence types. Considerable allelic variation among strains was identified among the single specificity subunit (hsdS) of each Type I R-M system, with a unique hsdS allele profile generally conserved within a monophyletic cluster of strains. Inactivating mutations were identified in Type I R-M systems of specific strains, showing heterogeneity in the complement of functional Type I R-M systems across X. fastidiosa. Genomic DNA methylation patterns were characterized in 20 X. fastidiosa strains and associated with Type I R-M system allele profiles. Overall, this study describes epigenetic modifications in X. fastidiosa associated with functional Type I R-M systems and characterizes the diversity in these systems across X. fastidiosa lineages.

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“…In comparison to their parent strain, the knockout of hsdM in BCG did not reveal a growth difference, while the knockout of hsdM in XDR-TB 11826 showed a drop in growth [ 21 ]. There were also some reports on the HsdM homolog in other bacterial species, such as in streptococci (e.g., S. pyogenes and S. agalactiae), which might involve bacterial drug resistance and other physiological features such as growth, hypoxia, and UV stress [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

DNA Methyltransferase HsdM Induce Drug Resistance on Mycobacterium tuberculosis via Multiple Effects

Chu

Zhang

et al. 2021

Antibiotics

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Besides the genomic variants, epigenetic mechanisms such as DNA methylation also have an effect on drug resistance. This study aimed to investigate the methylomes of totally/extensively drug-resistant M. tuberculosis clinical isolates using the PacBio single-molecule real-time technology. The results showed they were almost the same as the pan-susceptible ones. Genetics and bioinformatics analysis confirmed three DNA methyltransferases—MamA, MamB, and HsdM. Moreover, anti-tuberculosis drug treatment did not change the methylomes. In addition, the knockout of the DNA methyltransferase hsdM gene in the extensively drug-resistant clinical isolate 11826 revealed that the motifs of GTAYN4ATC modified by HsdM were completely demethylated. Furthermore, the results of the methylated DNA target analysis found that HsdM was mainly involved in redox-related pathways, especially the prodrug isoniazid active protein KatG. HsdM also targeted three drug-targeted genes, eis, embB, and gyrA, and three drug transporters (Rv0194, Rv1410, and Rv1877), which mildly affected the drug susceptibility. The overexpression of HsdM in M. smegmatis increased the basal mutation rate. Our results suggested that DNA methyltransferase HsdM affected the drug resistance of M. tuberculosis by modulating the gene expression of redox, drug targets and transporters, and gene mutation.

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Characterization of the Type I Restriction Modification System Broadly Conserved among Group A Streptococci

Cited by 22 publications

References 72 publications

Streptolysin O Deficiency in Streptococcus pyogenes M1T1 covR/S Mutant Strain Attenuates Virulence in In Vitro and In Vivo Infection Models

Streptolysin O Deficiency in Streptococcus pyogenes M1T1 covR/S Mutant Strain Attenuates Virulence in In Vitro and In Vivo Infection Models

Natural recombination among Type I restriction-modification systems creates diverse genomic methylation patterns among Xylella fastidiosa strains

DNA Methyltransferase HsdM Induce Drug Resistance on Mycobacterium tuberculosis via Multiple Effects

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