# Role of the Spx Regulator in Streptococcus mutans

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $375,000

## Abstract

Dental caries is a multi-faceted disease caused by interactions of cariogenic bacteria present in oral
biofilms with salivary components and dietary carbohydrates. Despite significant advances in our
understanding of the etiology and pathogenesis of this disease, dental caries remains the most prevalent and
costly biofilm-associated infection worldwide. Among the hundreds of bacterial species residing in the oral
biofilm, Streptococcus mutans has long been known as a primary cariogenic agent by its ability to drive the
ecological transition of the biofilm population from non-cariogenic to cariogenic. The capacities to synthesize a
thick extracellular polysaccharide matrix from sucrose, to generate copious amounts of lactic acid through
carbohydrate fermentation, and to rapidly adapt to environmental stresses are the key virulence attributes of S.
mutans. Although acidogenicity and aciduricity are well-established stress factors involved in virulence, the
ability to cope with endogenous and exogenous reactive oxygen species is also viewed as an important
attribute in the pathophysiology of S. mutans. This competing renewal has been set forth to study, at the
molecular and physiologic levels, the Spx oxidative stress regulators of S. mutans. The Spx protein is highly
conserved among Firmicutes and elegant studies with the Gram-positive paradigm Bacillus subtilis have
shown that it exerts positive control over oxidative stress genes through direct interactions with the RNA
polymerase and the promoter DNA region. Our work in the previous funding cycle identified two bona fide Spx
paralogs (SpxA1 and SpxA2) in the genome of S. mutans, and showed that stress tolerances and virulence are
significantly impaired in strains lacking one or both spx genes. Following our initial study, evidence of two Spx
regulatory systems emerged in other bacteria and the importance of Spx regulation to virulence has been
expanded to other streptococcal species. Although the spx gene has been well characterized in B. subtilis, the
interplay among two Spx paralogs and the scope of Spx regulation in pathogenic organisms such as S. mutans
are not well understood. The goals of this project are to understand the hierarchical relationship of the two Spx
paralogs and uncover novel, Spx regulated, antioxidant strategies in S. mutans. To accomplish these goals, we
propose three specific aims. In Aim 1, we will unravel the regulatory network controlling cellular abundance of
the Spx proteins. In the second aim, we will determine, at the molecular level, the regulatory capacities of each
Spx protein in relation to oxidative stress gene activation. In the third aim, we will take advantage of the
prominent role of SpxA1 in activation of oxidative stress responses to uncover how S. mutans respond to
peroxide stress at the metabolic level and to identify novel antioxidant pathways. The successful completion of
this project will provide new leads on bacterial processes that can be exploite...

## Key facts

- **NIH application ID:** 9952116
- **Project number:** 5R01DE019783-10
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Jose A Lemos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,000
- **Award type:** 5
- **Project period:** 2010-02-05 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952116

## Citation

> US National Institutes of Health, RePORTER application 9952116, Role of the Spx Regulator in Streptococcus mutans (5R01DE019783-10). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9952116. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*