K+ modulates genetic competence and the stress regulon of Streptococcus mutans

Binepal, Gursonika; Wenderska, Iwona B.; Crowley, Paula J.; Besingi, Richard N.; Senadheera, Dilani B.; Brady, L. Jeannine; Cvitkovitch, Dennis G.

doi:10.1099/mic.0.000458

Cited by 8 publications

(5 citation statements)

References 44 publications

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“…Control of K ϩ transport as an osmolyte by c-di-AMP has been shown to affect cell wall morphology (34), which may alter transformation. Previously, Binepal et al reported that in Streptococcus mutans transformation efficiency is reduced in medium containing low K ϩ or in a strain lacking Trk2, the major potassium transporter (40). Similarly, our work demonstrates that ΔtrkH pneumococci had a defect in transformation after incubation in a medium with low K ϩ .…”

Section: Discussionsupporting

confidence: 83%

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Bacterial Second Messenger Cyclic di-AMP Modulates the Competence State in Streptococcus pneumoniae

et al. 2020

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Streptococcus pneumoniae (the pneumococcus) is a naturally competent organism that causes diseases such as pneumonia, otitis media, and bacteremia. The essential bacterial second messenger cyclic di-AMP (c-di-AMP) is an emerging player in the stress responses of many pathogens. In S. pneumoniae, c-di-AMP is produced by a diadenylate cyclase, CdaA, and cleaved by phosphodiesterases Pde1 and Pde2. c-di-AMP binds a transporter of K+ (Trk) family protein, CabP, which subsequently halts K+ uptake via the transporter TrkH. Recently, it was reported that Pde1 and Pde2 are essential for pneumococcal virulence in mouse models of disease. To elucidate c-di-AMP-mediated transcription that may lead to changes in pathogenesis, we compared the transcriptomes of wild-type (WT) and Δpde1 Δpde2 strains by transcriptome sequencing (RNA-Seq) analysis. Notably, we found that many competence-associated genes are significantly upregulated in the Δpde1 Δpde2 strain compared to the WT. These genes play a role in DNA uptake, recombination, and autolysis. Competence is induced by a quorum-sensing mechanism initiated by the secreted factor competence-stimulating peptide (CSP). Surprisingly, the Δpde1 Δpde2 strain exhibited reduced transformation efficiency compared to WT bacteria, which was c-di-AMP dependent. Transformation efficiency was also directly related to the [K+] in the medium, suggesting a link between c-di-AMP function and the pneumococcal competence state. We found that a strain that possesses a V76G variation in CdaA produced less c-di-AMP and was highly susceptible to CSP. Deletion of cabP and trkH restored the growth of these bacteria in medium with CSP. Overall, our study demonstrates a novel role for c-di-AMP in the competence program of S. pneumoniae. IMPORTANCE Genetic competence in bacteria leads to horizontal gene transfer, which can ultimately affect antibiotic resistance, adaptation to stress conditions, and virulence. While the mechanisms of pneumococcal competence signaling cascades have been well characterized, the molecular mechanism behind competence regulation is not fully understood. The bacterial second messenger c-di-AMP has previously been shown to play a role in bacterial physiology and pathogenesis. In this study, we provide compelling evidence for the interplay between c-di-AMP and the pneumococcal competence state. These findings not only attribute a new biological function to this dinucleotide as a regulator of competence, transformation, and survival under stress conditions in pneumococci but also provide new insights into how pneumococcal competence is modulated.

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Section: Discussionsupporting

confidence: 83%

“…A study on competence in Streptococcus mutans reported that both a concentration of at least 25 mM environmental K ϩ and a potassium transporter, Trk2, were required for competence development and efficient transformation (40). Therefore, we hypothesized that high c-di-AMP levels diminishing K ϩ uptake may be impeding transformation.…”

Section: Resultsmentioning

confidence: 98%

Bacterial Second Messenger Cyclic di-AMP Modulates the Competence State in Streptococcus pneumoniae

et al. 2020

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“…This secretory protein serves as an apparent negative regulator of biofilm cell density and genetic competence (59). Its production is associated with K + availability and influenced by growth phase (62).…”

Section: Biofilm Formationmentioning

confidence: 99%

The Biology of Streptococcus mutans

et al. 2019

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As a major etiological agent of human dental caries, Streptococcus mutans resides primarily in biofilms that form on the tooth surfaces, also known as dental plaque. In addition to caries, S. mutans is responsible for cases of infective endocarditis with a subset of strains being indirectly implicated with the onset of additional extraoral pathologies. During the past 4 decades, functional studies of S. mutans have focused on understanding the molecular mechanisms the organism employs to form robust biofilms on tooth surfaces, to rapidly metabolize a wide variety of carbohydrates obtained from the host diet, and to survive numerous (and frequent) environmental challenges encountered in oral biofilms. In these areas of research, S. mutans has served as a model organism for ground-breaking new discoveries that have, at times, challenged long-standing dogmas based on bacterial paradigms such as Escherichia coli and Bacillus subtilis . In addition to sections dedicated to carbohydrate metabolism, biofilm formation, and stress responses, this article discusses newer developments in S. mutans biology research, namely, how S. mutans interspecies and cross-kingdom interactions dictate the development and pathogenic potential of oral biofilms and how next-generation sequencing technologies have led to a much better understanding of the physiology and diversity of S. mutans as a species.

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“…The mid‐exponential profiles failed to explain changes in acid tolerance displayed by the srtA deleted strain, which led us to assume that the acute acid tolerance of △ srtA may be acquired from a post‐transcriptional regulation after lethal acid shock; another possible explanation is that its intrinsic acid tolerance is enhanced through the loss of srtA , that is, the aciduricity of △ srtA is strengthened even in non‐acidic environments. Transcriptional data from the stationary phase partially confirmed this hypothesis by showing increased transcriptional abundances of acid tolerance related genes including the F 1 ‐F 0 ‐ATPase encoding atp operon ( atpABCDEFGH ), the potassium transport system Trk2 encoding trk operon ( trkB , trkA , pacL ), BCAA formation‐related genes ( leuACD , ilvE ), the agmatine deiminase relating agu operon ( aguRBDAC ), and the acylphosphatase encoding smu_1725 (Baker et al, ; Binepal et al, , ; Griswold, Chen, & Burne, ; Rice, Turner, Carney, Gu, & Ahn, ; Santiago, MacGilvray, Faustoferri, & Quivey, ; Zhang et al, ). These highly induced acid tolerance involved operons and genes, might impart stronger aciduricity to △ srtA under neutral growth conditions, but the reason why survivals of the sublethal pH stimulated △ srtA were less than those of the adapted UA159 and complementary strains in the acid‐killing assay is still under exploration.…”

Section: Discussionmentioning

confidence: 82%

Sortase A‐mediated modification of the Streptococcus mutans transcriptome and virulence traits

Chen

Liu

Peng

et al. 2019

Molecular Oral Microbiology

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Sortase A contributes to adhesion and biofilm formation of Streptococcus mutans by anchoring surface proteins like P1 onto the cell wall, and few other functional characterization has been annotated to this protein and its coding gene srtA. In this study we investigated that whether srtA deletion would affect S. mutans virulence determinants in addition to adhesion and further explored whether these effects were caused due to changes in S. mutans genomic transcription. We used acid‐killing assays, glycolytic rate assessments, and exopolysaccharide (EPS) formation tests to detect whether srtA deletion influenced S. mutans acid tolerance/production and glucan formation. Comparisons between RNA‐sequencing data from both the exponential and stationary phases of UA159 and the srtA‐deleted strain were made to determine the impact of srtA knockout on S. mutans genomic transcription. Results of our assays indicated that S. mutans aciduricity was enhanced in the srtA deleted strain when bacterial cells were directly subjected to pH 2.8, but the enhancement was repressed when the acid tolerance response was induced in advance. The srtA mutation strain exhibited reduced EPS formation in mature biofilms. SrtA deletion led to pleiotropic changes in the S. mutans transcriptome with a growth phase‐dependent pattern. The affected genes mainly included those involved in aciduricity, carbohydrate transport, and EPS formation. It was concluded that S. mutans srtA exhibited multiple effects on the virulence traits of this pathogen, including acid tolerance and glucan formation, and that these alterations could be partially due to transcriptional changes upon loss of srtA.

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K+ modulates genetic competence and the stress regulon of Streptococcus mutans

Cited by 8 publications

References 44 publications

Bacterial Second Messenger Cyclic di-AMP Modulates the Competence State in Streptococcus pneumoniae

Bacterial Second Messenger Cyclic di-AMP Modulates the Competence State in Streptococcus pneumoniae

The Biology of Streptococcus mutans

Sortase A‐mediated modification of the Streptococcus mutans transcriptome and virulence traits

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