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Updated: Jun 6, 2025

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Published on: March 10, 2017
The group A Streptococcus pathogenicity island RD2: virulence role and barriers to conjugative transfer
Roshika Roshika1, Sushila Baral1, Ira Jain1
1Department of Microbiology & Immunology, Reno School of Medicine, University of Nevada, Reno, Nevada, USA.
Abstract:
Serotype M28 isolates of the bacterial pathogen the group A Streptococcus (GAS; Streptococcus pyogenes), but not isolates of other serotypes, have a nonrandom association with cases of puerperal sepsis, a life-threatening infection that can occur in women following childbirth. In prior studies, we established that RD2, a pathogenicity island present in all M28 GAS isolates but mostly absent from other serotypes, is a factor in the M28-puerperal sepsis association. Here, we identified a significant reduction in the RD2 conjugation frequency in inter-serotype conjugation assays relative to intra-serotype assays. As isolates of most GAS serotypes produce an antiphagocytic hyaluronic acid capsule, while M28 isolates do not, we tested whether the capsule served as a barrier to RD2 acquisition or maintenance. The data showed that capsule production had no impact on the RD2 conjugation frequency or on the ability of RD2 to enhance vaginal colonization by GAS, but did inhibit the ability of RD2 to enhance GAS adherence to vaginal epithelial cell lines. Further molecular explanations for the inter-serotype barrier to RD2 conjugative transfer were investigated, and a conserved, chromosomally encoded Type I restriction-modification system was identified as being key. We also identified that RD2 modifies the GAS transcriptome, including mRNAs encoding virulence factors with adherence and dissemination roles, following exposure to human plasma. Our data provide insights into factors that contribute to the restriction of the RD2 pathogenicity island to discrete subsets of the GAS population.
Insights
Serotype M28 group A Streptococcus (GAS) isolates are linked to puerperal sepsis. A pathogenicity island, RD2, is restricted due to a Type I restriction-modification system, not capsule presence.
Area of Science:
- Microbiology
- Genetics
- Infectious Diseases
Background:
- Serotype M28 group A Streptococcus (GAS) isolates show a strong association with puerperal sepsis.
- The RD2 pathogenicity island is present in M28 GAS but largely absent in other serotypes, suggesting its role in this association.
Purpose of the Study:
- To investigate the factors restricting the spread of the RD2 pathogenicity island between different GAS serotypes.
- To understand how RD2 influences GAS virulence and its association with puerperal sepsis.
Main Methods:
- Conjugation assays were performed to assess RD2 transfer frequency between GAS serotypes.
- The role of the hyaluronic acid capsule in RD2 acquisition and GAS virulence was evaluated.
- A Type I restriction-modification system was identified as a key factor in inter-serotype transfer restriction.
- Transcriptomic analysis was used to study RD2's effect on GAS gene expression.
Main Results:
- RD2 conjugation frequency was significantly reduced in inter-serotype assays compared to intra-serotype assays.
- The hyaluronic acid capsule did not affect RD2 conjugation frequency or vaginal colonization but inhibited adherence.
- A conserved, chromosomally encoded Type I restriction-modification system was identified as the primary barrier to RD2 transfer.
- RD2 was found to alter the GAS transcriptome, affecting virulence factors involved in adherence and dissemination upon exposure to human plasma.
Conclusions:
- The Type I restriction-modification system is a crucial factor limiting the spread of the RD2 pathogenicity island to specific GAS serotypes.
- Understanding these genetic barriers provides insights into the population structure of GAS and the evolution of virulence.
- The findings contribute to understanding the specific association of M28 GAS with puerperal sepsis.
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