Acetate and Potassium Modulate the Stationary-Phase Activation of lrgAB in Streptococcus mutans

Ahn, Sang‐Joon; Desai, Shailja; Blanco, Loraine; Lin, Min; Rice, Kelly C.

doi:10.3389/fmicb.2020.00401

Cited by 6 publications

(26 citation statements)

References 62 publications

(97 reference statements)

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“…Our recent study showed that the magnitude of lrgAB induction and pyruvate flux depends on the growth medium [27]. In this previous study, we demonstrated that stationary phase lrgAB induction and pyruvate uptake are completely blocked in TV11, suggesting that TV medium provides a different environment from FMC.…”

Section: Tv Medium Provides a More Favorable Environment For Responsementioning

confidence: 83%

“…Another linkage between the Pta-AckA pathway and pyruvate uptake regulation may be related to the extracellular level of acetate, the major end product of the Pta-AckA pathway which is excreted as another overflow metabolite during growth to eliminate extra redox potential when glucose is no longer oxidized to CO 2 . We recently demonstrated that external acetate can enhance stationary phase lrgAB induction and inhibit growth in excess [27], suggesting that acetate may mediate the response of lrgAB to the stationary phase, as well as cell lysis and death. Although the disruption of the Pta-AckA pathway inhibits acetate production, lack of acetate does not seem to directly result in the observed dramatic reduction of lrgAB induction and pyruvate uptake, because the inhibitory effect of an inactive Pta-AckA pathway on lrgAB induction was observed in both FMC11 (acetate-enriched) and TV3 (acetate-limited).…”

Section: Discussionmentioning

confidence: 99%

“…In this context, interest in bacterial pyruvate flux and regulation is emerging, due to the following facts: pyruvate directs the key metabolic fluxes for growth and energy generation [11][12][13]; it is excreted as an overflow metabolite during growth and is reabsorbed during starvation [14][15][16][17]; it can promote growth of metabolically inactive stationary phase cells [18][19][20][21]; and it buffers external sources of oxidative stress, i.e., as an H 2 O 2 -scavenger [22][23][24][25]. These features of pyruvate have also been reported in S. mutans [26,27].…”

Section: Introductionmentioning

confidence: 91%

“…Acetyl-CoA is then metabolized to acetate by the Pta-AckA pathway with the production of one molecule of ATP [37]. We recently revealed that the genes encoding the key enzymes (Pta, phosphate acetyltransferase and AckA, acetate kinase) of the Pta-AckA pathway were significantly upregulated during the transition to stationary phase in BHI and FMC11 (lrgAB-inducible) but not in TV11 (lrgAB-noninducible) [27]. Therefore, we assumed that the Pta-AckA pathway may participate in the regulation of lrgAB, especially in this glucose-limiting condition.…”

Section: Inactivation Of the Pta-acka Pathway Completely Inhibits Stamentioning

confidence: 99%

“…When glucose concentration is low, pyruvate is converted to acetyl-CoA and formate by Pfl (pyruvate formate lyase) or acetyl-CoA and CO 2 by the Pdh (pyruvate dehydrogenase) complex, depending on the absence or presence of oxygen, respectively. In fact, our previous studies suggested a strong correlation between Pdh/Pfl and lrgAB regulation, because pdhC and pfl were also significantly upregulated at the early stationary phase, compared to that of the early exponential phase [27,28]. To test for a role of Pdh or Pfl in lrgAB regulation, we attempted to mutate the gene(s) encoding Pdh or Pfl.…”

Section: Pfl Is Involved In the Regulation Of Lrgab Expressionmentioning

confidence: 99%

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The Pta-AckA Pathway Regulates LrgAB-Mediated Pyruvate Uptake in Streptococcus mutans

et al. 2020

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Pyruvate forms the central node of carbon metabolism and promotes growth as an alternative carbon source during starvation. We recently revealed that LrgAB functions as a stationary phase pyruvate uptake system in Streptococcus mutans, the primary causative agent of human dental caries, but its underlying regulatory mechanisms are still not clearly understood. This study was aimed at further characterizing the regulation of LrgAB from a metabolomic perspective. We utilized a series of GFP quantification, growth kinetics, and biochemical assays. We disclosed that LrgAB is critical for pyruvate uptake especially during growth under low-glucose stress. Inactivation of the Pta-Ack pathway, responsible for the conversion of acetyl-CoA to acetate, completely inhibits stationary phase lrgAB induction and pyruvate uptake, and renders cells insensitive to external pyruvate as a signal. Inactivation of Pfl, responsible for the conversion of pyruvate to acetyl-CoA under anaerobic conditions, also affected stationary phase pyruvate uptake. This study explores the metabolic components of pyruvate uptake regulation through LrgAB, and highlights its potential as a metabolic stimulator, contributing to the resuscitation and survival of S. mutans cells during nutritional stress.

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Section: Tv Medium Provides a More Favorable Environment For Responsementioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Inactivation Of the Pta-acka Pathway Completely Inhibits Stamentioning

confidence: 99%

Section: Pfl Is Involved In the Regulation Of Lrgab Expressionmentioning

confidence: 99%

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The Pta-AckA Pathway Regulates LrgAB-Mediated Pyruvate Uptake in Streptococcus mutans

et al. 2020

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Protein expression profiling, in silico classification and pathway analysis of cariogenic bacteria Streptococcus mutans under bacitracin stress conditions

Zaidi

Aswal

Kumar

et al. 2022

Journal of Medical Microbiology

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Introduction. Streptococcus mutans is a cariogenic bacterium that causes dental caries as well as being implicated in other dental pathologies and infective endocarditis. Bacitracin is a bactericidal antibiotic that induces cell wall stress in Gram-positive bacteria. Gap Statement. S. mutans is among the most characterized Gram-positive bacteria. However, the transcriptome and proteome of S. mutans have received less attention, and they are actually key in understanding the pathogenesis of any bacteria. In this study, we extracted the whole proteome of S. mutans grown under bacitracin stress. Such a proteome is anticipated to offer deep insights related to physiological dynamic fluctuations and, consequently, it may provide ‘proteomic signatures’ to be identified as potential targets. Aim. The aim of the study is to explore the general stress response that S. mutans exhibits at the proteome level when cell wall stress is imposed on it. Methodology. A sub-MIC concentration of bacitracin was added to the growth media of S. mutans followed by whole-cell protein extraction. The proteome was then subjected to high-throughput proteomics analysis, i.e. liquid chromatography tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins obtained through LC-MS/MS underwent analyses such as gene ontology, KEGG (Kyoto Encyclopaedia of Genes and Genomes) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analysis, and STRING for functional annotation, pathway enrichment and protein–protein interaction (PPI) networks, respectively. These proteins were also categorized into functional classes using the PANTHER (Protein Annotation Through Evolutionary Relationship) classification system. Result. LC-MS/MS produced data from 321 identified proteins. From these, 41 and 30 were found to be significantly over- (≥2 fold change) and underexpressed (≤0.4 fold change), respectively. In the upregulated proteins we mostly observed sortases and proteins involved in the EPS biosynthesis pathway, whereas among the downregulated proteins the majority related to glycolysis. Conclusion. The sortase family of proteins appear to be potential targets because they regulate various virulence factors and therefore can be targeted to inhibit multiple virulence pathways simultaneously. This study offers an understanding of proteomic fluctuations in response to cell wall stress and can thus help in identifying key players mediating virulence.

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Glucose PTS Modulates Pyruvate Metabolism, Bacterial Fitness, and Microbial Ecology in Oral Streptococci

Zeng

Walker

Burne

et al. 2022

Preprint

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Spontaneous mutants with defects in the primary glucose phosphotransferase (PTS) permease (manLMNO) of Streptococcus sanguinis SK36 showed enhanced fitness at low pH. Transcriptomics and metabolomics with a manL deletion mutant (SK36/manL) revealed redirection of pyruvate to production of acetate and formate, rather than lactate. The observations were consistent with measurements of decreased lactic acid accumulation and increased excretion of pyruvate and H2O2. Genes showing increased expression in SK36/manL included those encoding carbohydrate transporters, extracellular glycosidases, intracellular polysaccharide (IPS) metabolism, arginine deiminase, and pathways for metabolism of acetoin, ethanolamine, ascorbate and formate; along with genes required for membrane biosynthesis and adhesion. Streptococcus mutans UA159 persisted much better in biofilm co-cultures with SK36/manL than with SK36, an effect that was further enhanced by culturing the biofilms anaerobically but dampened by adding arginine to the medium. We posited that the enhanced persistence of S. mutans with SK36/manL was in part due to excess excretion of pyruvate by the latter, as addition of pyruvate to S. mutans-S. sanguinis co-cultures increased the proportions of UA159 in the biofilms. Reduction of the buffer capacity or increasing the concentration of glucose benefited UA159 when co-cultured with SK36, but not with SK36/manL; likely due to the altered metabolism and enhanced acid tolerance of the mutant. When manL was deleted in S. mutans or Streptococcus gordonii, the mutants presented altered fitness characteristics. Our study demonstrated that PTS-dependent modulation of central metabolism can profoundly affect streptococcal fitness and metabolic interactions, revealing another dimension in commensal-pathogen relationships influencing dental caries development.

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Acetate and Potassium Modulate the Stationary-Phase Activation of lrgAB in Streptococcus mutans

Cited by 6 publications

References 62 publications

The Pta-AckA Pathway Regulates LrgAB-Mediated Pyruvate Uptake in Streptococcus mutans

The Pta-AckA Pathway Regulates LrgAB-Mediated Pyruvate Uptake in Streptococcus mutans

Protein expression profiling, in silico classification and pathway analysis of cariogenic bacteria Streptococcus mutans under bacitracin stress conditions

Glucose PTS Modulates Pyruvate Metabolism, Bacterial Fitness, and Microbial Ecology in Oral Streptococci

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