Dataset Information

Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae.

ABSTRACT: Restriction-Modification systems (RMS) are one of the main mechanisms of defence against foreign DNA invasion and can have an important role in the regulation of gene expression. The obligate human pathogen Neisseria gonorrhoeae carries one of the highest loads of RMS in its genome; between 13 to 15 of the three main types. Previous work has described their organization in the reference genome FA1090 and has inferred the associated methylated motifs. Here, we studied the structure of RMS and target methylated motifs in 25 gonococcal strains sequenced with Single Molecule Real-Time (SMRT) technology, which provides data on DNA modification. The results showed a variable picture of active RMS in different strains, with phase variation switching the activity of Type III RMS, and both the activity and specificity of a Type I RMS. Interestingly, the Dam methylase was found in place of the NgoAXI endonuclease in two of the strains, despite being previously thought to be absent in the gonococcus. We also identified the real methylation target of NgoAXII as 5'-GCAGA-3', different from that previously described. Results from this work give further insights into the diversity and dynamics of RMS and methylation patterns in N. gonorrhoeae.

SUBMITTER: Sanchez-Buso L

PROVIDER: S-EPMC6789123 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae.

Sánchez-Busó Leonor L Golparian Daniel D Parkhill Julian J Unemo Magnus M Harris Simon R SR

Scientific reports 20191011 1

Restriction-Modification systems (RMS) are one of the main mechanisms of defence against foreign DNA invasion and can have an important role in the regulation of gene expression. The obligate human pathogen Neisseria gonorrhoeae carries one of the highest loads of RMS in its genome; between 13 to 15 of the three main types. Previous work has described their organization in the reference genome FA1090 and has inferred the associated methylated motifs. Here, we studied the structure of RMS and tar ...[more]

PMID: 31605008

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Project description:Knowledge of within-host genetic variation informs studies on transmission dynamics. We studied within-host genetic variation in Neisseria gonorrhoeae over the course of infection and across different anatomical locations. Isolates were obtained during a clinical trial, and isolates from consecutive time points reflected persistent infections after treatment failure. We compared sequence types (STs) and recombination unfiltered- and filtered core genome single nucleotide polymorphism (SNP) distances in 65 within-host isolate pairs from the same anatomical location over time-obtained with a median interval of 7 days-and 65 isolate pairs across different anatomical locations at one time point. Isolates with different Multi-Locus Sequence Types (MLST), NG-Sequence Types for Antimicrobial Resistance (NG-STAR) and NG-Multi Antigen Sequence Types (NG-MAST) had a median of 1466 recombination filtered SNPs, whereas a median of 1 SNP was found between isolates with identical STs or a different NG-MAST only. The threshold for differentiating between strains was set at 10 recombination filtered SNPs, showing that isolates from persistent infections could have different NG-MASTs. Antibiotic pressure applied through treatment did not lead to an increase in genetic variation in specific genes or in overall extent of variation, compared to variation across anatomical locations. Instead, within-host genetic variation was proposedly driven by the host immune response, as it was concentrated in genomic regions encoding surface exposed proteins involved in host-microbe interaction. Ultimately, 15/228 (6.5%) between-host pairs contained a single strain, suggesting between-host transmission. However, patient reported data are needed to differentiate within-host persistence from between-host transmission. IMPORTANCE Understanding transmission dynamics of Neisseria gonorrhoeae (Ng) is based on the identification of transmission events. These can be identified by assessing genetic relatedness between Ng isolates, expressed as core genome SNP distances. However, a SNP threshold to differentiate between strains needs to be defined, using knowledge on within- and between-host genetic variation. Here, we assessed within-host genetic variation, using a unique set of within-host Ng isolates from the same anatomical location over time or across different anatomical locations at one time point. The insights in genetic variation that occurred during the infection period contribute to the understanding of infection dynamics. In addition, the obtained knowledge can be used for future research on transmission dynamics and development of public health interventions based on bacterial genomic data.

Dataset Information

Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae.

Publications

Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae.

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