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The Streptococcus mutans irvA gene encodes a trans-acting riboregulatory mRNA.

ABSTRACT: In both prokaryotes and eukaryotes, insight into gene function is typically obtained by in silico homology searches and/or phenotypic analyses of strains bearing mutations within open reading frames. However, the studies herein illustrate how mRNA function is not limited to the expression of a cognate protein. We demonstrate that a stress-induced protein-encoding mRNA (irvA) from the dental caries pathogen Streptococcus mutans directly modulates target mRNA (gbpC) stability through seed pairing interactions. The 5' untranslated region of irvA mRNA is a trans riboregulator of gbpC and a critical activator of the DDAG stress response, whereas IrvA functions independently in the regulation of natural competence. The irvA riboregulatory domain controls GbpC production by forming irvA-gbpC hybrid mRNA duplexes that prevent gbpC degradation by an RNase J2-mediated pathway. These studies implicate a potentially ubiquitous role for typical protein-encoding mRNAs as riboregulators, which could alter current concepts in gene regulation.

SUBMITTER: Liu N

PROVIDER: S-EPMC5663275 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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The Streptococcus mutans irvA gene encodes a trans-acting riboregulatory mRNA.

Liu Nan N Niu Guoqing G Xie Zhoujie Z Chen Zhiyun Z Itzek Andreas A Kreth Jens J Gillaspy Allison A Zeng Lin L Burne Robert R Qi Fengxia F Merritt Justin J

Molecular cell 20150101 1

In both prokaryotes and eukaryotes, insight into gene function is typically obtained by in silico homology searches and/or phenotypic analyses of strains bearing mutations within open reading frames. However, the studies herein illustrate how mRNA function is not limited to the expression of a cognate protein. We demonstrate that a stress-induced protein-encoding mRNA (irvA) from the dental caries pathogen Streptococcus mutans directly modulates target mRNA (gbpC) stability through seed pairing ...[more]

PMID: 25574948

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Project description:The cariogenic pathogen Streptococcus mutans effectively utilizes dietary sucrose for the synthesis of exopolysaccharide, which act as a scaffold for its biofilm, thus contributing to its pathogenicity, environmental stress tolerance, and antimicrobial resistance. The two-component system VicRK of S. mutans regulates a group of virulence genes that are associated with biofilm matrix synthesis. Knockout of vicX affects biofilm formation, oxidative stress tolerance, and transformation of S. mutans. However, little is known regarding the vicX-modulated structural characteristics of the exopolysaccharides underlying the biofilm formation and the phenotypes of the vicX mutants. Here, we identified the role of vicX in the structural characteristics of the exopolysaccharide matrix and biofilm physiology. The vicX mutant (SmuvicX) biofilms seemingly exhibited "desertification" with architecturally impaired exopolysaccharide-enmeshed cell clusters, compared with the UA159 strain (S. mutans wild type strain). Concomitantly, SmuvicX showed a decrease in water-insoluble glucan (WIG) synthesis and in WIG/water-soluble glucan (WSG) ratio. Gel permeation chromatography (GPC) showed that the WIG isolated from the SmuvicX biofilms had a much lower molecular weight compared with the UA159 strain indicating differences in polysaccharide chain lengths. A monosaccharide composition analysis demonstrated the importance of the vicX gene in the glucose metabolism. We performed metabolite profiling via (1)H nuclear magnetic resonance spectroscopy, which showed that several chemical shifts were absent in both WSG and WIG of SmuvicX biofilms compared with the UA159 strain. Thus, the modulation of structural characteristics of exopolysaccharide by vicX provides new insights into the interaction between the exopolysaccharide structure, gene functions, and cariogenicity. Our results suggest that vicX gene modulates the structural characteristics of exopolysaccharide associated with cariogenicity, which may be explored as a potential target that contributes to dental caries management. Furthermore, the methods used to purify the EPS of S. mutans biofilms and to analyze multiple aspects of its structure (GPC, gas chromatography-mass spectrometry, and (1)H nuclear magnetic resonance spectroscopy) may be useful approaches to determine the roles of other virulence genes for dental caries prevention.

Project description:Early childhood caries (ECC) is a chronic disease affecting the oral health of children globally. This disease is multifactorial, but a primary factor is cariogenic microorganisms such as Streptococcus mutans. Biosynthetic gene clusters (BGCs) encode small molecules with diverse biological activities that influence the development of many microbial diseases, including caries. The purpose of this study was to identify BGCs in S. mutans from a high-caries risk study population using whole-genome sequencing and assess their association with ECC. Forty representative S. mutans isolates were selected for genome sequencing from a large-scale epidemiological study of oral microbiology and dental caries in children from a localized Alabama population. A total of 252 BGCs were identified using the antiSMASH BGC-mining tool. Three types of BGCs identified herein-butyrolactone-like, ladderane-like, and butyrolactone-ladderane-like hybrid (BL-BGC)-have not been reported in S. mutans. These 3 BGCs were cross-referenced against public transcriptomics data, and were found to be highly expressed in caries subjects. Furthermore, based on a polymerase chain reaction screening for core BL genes, 93% of children with BL-BGC had ECC. The role of BL-BGC was further investigated by examining cariogenic traits and strain fitness in a deletion mutant using in vitro biofilm models. Deletion of the BL-BGC significantly increased biofilm pH as compared to the parent strain, while other virulence and fitness properties remained unchanged. Intriguingly, BL-BGC containing strains produced more acid, a key cariogenic feature, and less biofilm than the model cariogenic strain S. mutans UA159, suggesting the importance of this BL-BGC in S. mutans-mediated cariogenesity. The structure of any BL-BGC derived metabolites, their functions, and mechanistic connection with acid production remain to be elucidated. Nevertheless, this study is the first to report the clinical significance of a BL-BGC in S. mutans. This study also highlights pangenomic diversity, which is likely to affect phenotype and virulence.

Dataset Information

The Streptococcus mutans irvA gene encodes a trans-acting riboregulatory mRNA.

Publications

The Streptococcus mutans irvA gene encodes a trans-acting riboregulatory mRNA.

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