# The variable disease potential of group A Streptococcus isolates: a link to puerperal infections

> **NIH NIH R21** · UNIVERSITY OF NEVADA RENO · 2020 · $178,271

## Abstract

PROJECT SUMMARY
Pregnant and post-partum women have a 20-fold increase in the incidence of invasive group A Streptococcus
(GAS) infections compared with non-pregnant women, with this mostly being attributable to infections that
originate in the reproductive tract ante- or post-partum (aka puerperal infections). Decades of epidemiological
data have identified that serotype M28 GAS isolates, for undefined reasons, are non-randomly associated with
puerperal infections. The goal of the proposed research is to characterize the function and transfer of a
36.3 kb genomic island, termed the ‘region of difference 2’ (RD2), with regard to the enhanced ability of
serotype M28 GAS isolates to cause puerperal infections. This research will be of interest to the infectious
diseases community because of the following observations. First, RD2 is distributed in the GAS population
along serotype-specific lines, being present in all serotype M28 GAS strains but absent from most other
serotypes. Second, sequence analysis of RD2 is consistent with this element being horizontally transferred
into GAS from group B Streptococci (GBS), an important finding given that GBS are a common constituent of
the vaginal microflora. Third, RD2-like elements are also present in other pathogens (e.g. group C and G
Streptococci), expanding the relevance of the insights gained.
Specific Aim 1: Assess the role of the GAS hyaluronic acid capsule in the function and transfer of the
RD2 element. We have identified that the RD2 element enhances the ability of serotype M28 GAS to adhere
to human vaginal epithelial cell lines and to colonize the female reproductive tract. Given the phenotype-
altering consequences of harboring RD2 we believe it prudent to assess factors responsible for the transfer
and function of this element in the GAS population. We will test the hypothesis that, by masking the GAS cell
surface, the hyaluronic acid capsule inhibits both the cell-to-cell transfer and phenotype-altering activity of
RD2. This hypothesis is supported by the recent finding that serotype M28 isolates are acapsular.
Specific Aim 2: Determine whether RD2 promotes invasive GAS disease and identify the molecular
basis behind the RD2-mediated remodeling of transcript levels. In the first part of this aim, we will test the
hypothesis that the RD2 element promotes invasive GAS disease in addition to promoting host colonization. In
the second part of this aim, we will test the hypothesis that the activity of RD2-encoded transcriptional and
post-transcriptional regulators are behind our finding that transcripts from 108 core chromosomal genes (i.e.
genes located outside of RD2) are altered in their abundance in the presence of RD2.
Completion of this proposal will advance our understanding of strain emergence and phenotypic heterogeneity
in a prevalent Gram-positive pathogen. Specifically, the data would inform on the intimate relationship
between RD2 and GAS isolates, providing a link between GAS gene c...

## Key facts

- **NIH application ID:** 9873474
- **Project number:** 1R21AI148813-01
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** Paul Sumby
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $178,271
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873474

## Citation

> US National Institutes of Health, RePORTER application 9873474, The variable disease potential of group A Streptococcus isolates: a link to puerperal infections (1R21AI148813-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9873474. Licensed CC0.

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