Microfluidic study of competence regulation in <i>Streptococcus mutans</i>: environmental inputs modulate bimodal and unimodal expression of <i>comX</i>

Son, Minjun; Ahn, Sang‐Joon; Guo, Qiang; Burne, Robert A.; Hagen, Stephen J.

doi:10.1111/j.1365-2958.2012.08187.x

Cited by 99 publications

(279 citation statements)

References 46 publications

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“…Cells that were attached to C. albicans as well as more distant biofilm cells were fluorescing. Such unimodal induction of sigX has previously only been demonstrated in pure cultures of S. mutans in a peptidefree chemically defined medium (Son et al, 2012). Here, we show that in a semi-defined medium, unimodal activation of SigX occurs if the two Interactions in dual-species biofilms H Sztajer et al species C. albicans and S. mutans are grown together.…”

Section: Cultivation Mediummentioning

confidence: 62%

Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans

et al. 2014

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Polymicrobial biofilms are of large medical importance, but relatively little is known about the role of interspecies interactions for their physiology and virulence. Here, we studied two human pathogens co-occuring in the oral cavity, the opportunistic fungus Candida albicans and the caries-promoting bacterium Streptococcus mutans. Dual-species biofilms reached higher biomass and cell numbers than mono-species biofilms, and the production of extracellular polymeric substances (EPSs) by S. mutans was strongly suppressed, which was confirmed by scanning electron microscopy, gas chromatography-mass spectrometry and transcriptome analysis. To detect interkingdom communication, C. albicans was co-cultivated with a strain of S. mutans carrying a transcriptional fusion between a green fluorescent protein-encoding gene and the promoter for sigX, the alternative sigma factor of S. mutans, which is induced by quorum sensing signals. Strong induction of sigX was observed in dual-species biofilms, but not in single-species biofilms. Conditioned media from mixed biofilms but not from C. albicans or S. mutans cultivated alone activated sigX in the reporter strain. Deletion of comS encoding the synthesis of the sigX-inducing peptide precursor abolished this activity, whereas deletion of comC encoding the competence-stimulating peptide precursor had no effect. Transcriptome analysis of S. mutans confirmed induction of comS, sigX, bacteriocins and the downstream late competence genes, including fratricins, in dual-species biofilms. We show here for the first time the stimulation of the complete quorum sensing system of S. mutans by a species from another kingdom, namely the fungus C. albicans, resulting in fundamentally changed virulence properties of the caries pathogen.

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Section: Cultivation Mediummentioning

confidence: 62%

Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans

et al. 2014

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“…When S. mutans is grown in a chemically defined medium (CDM) with the addition of synthetic XIP, competence activation through the ComRS signaling system is superior, involving nearly the entire population (10,18,19). However, XIP appears to be inactive and only CSP induces competence when S. mutans is grown in a complex medium (18,20). This phenomenon is interpreted as bimodal behav-ior of S. mutans in response to a signaling peptide due to the change in medium components (20).…”

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confidence: 99%

MecA Protein Acts as a Negative Regulator of Genetic Competence in Streptococcus mutans

et al. 2013

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c Streptococcus mutans develops competence for genetic transformation through a complex network that receives inputs from at least two signaling peptides, competence-stimulating peptide (CSP) and sigX-inducing peptide (XIP). The key step of competence induction is the transcriptional activation of comX, which encodes an alternative sigma factor, SigX ( X ), controlling the expression of late competence genes essential for DNA uptake and recombination. In this study, we provide evidence that MecA acts as a negative regulator in the posttranslational regulation of SigX in S. mutans. Using luxAB transcriptional reporter strains, we demonstrate that MecA represses the expression of late competence genes in S. mutans grown in a complex medium that is subpermissive for competence induction by CSP. The negative regulation of competence by MecA requires the presence of a functional SigX. Accordingly, inactivation of MecA results in a prolonged competence state of S. mutans under this condition. We have also found that the AAA؉ protease ClpC displays a similar repressing effect on late competence genes, suggesting that both MecA and ClpC function coordinately to regulate competence in the same regulatory circuit in S. mutans. This suggestion is strongly supported by the results of bacterial two-hybrid assays, which demonstrate that MecA interacts with both SigX and ClpC, forming a ternary SigX-MecA-ClpC complex. Western blot analysis also confirms that inactivation of MecA or ClpC results in the intracellular accumulation of the SigX in S. mutans. Together, our data support the notion that MecA mediates the formation of a ternary SigX-MecA-ClpC complex that sequesters SigX and thereby negatively regulates genetic competence in S. mutans.

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“…When Streptococcus mutans is grown in CDM, competence activation through the ComRS system is superior, nearly involving the entire population [5,16]. However, XIP appears to be inactive when Streptococcus mutans is grown in a complex medium [5,[16][17][18]. This phenomenon is interpreted as a bimodal behavior of Streptococcus mutans in response to different signaling peptides due to changes in medium components [18].…”

Section: Introductionmentioning

confidence: 93%

“…However, XIP appears to be inactive when Streptococcus mutans is grown in a complex medium [5,[16][17][18]. This phenomenon is interpreted as a bimodal behavior of Streptococcus mutans in response to different signaling peptides due to changes in medium components [18]. Importantly, such bimodal behavior requires the presence of intact comS that encodes the precursor of XIP.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, it becomes clear that Streptococcus mutans can finely regulate genetic competence via a complex regulatory network that receives and responds inputs from at least two signaling peptides, CSP and XIP, dependently on growth conditions. The key step of competence induction by either of these signaling peptides is transcriptional activation of comX that controls expression of late competence genes for DNA transport, uptake and recombination [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Proteolytic Regulation of Competence Development in the Genus Streptococcus: Implications in Competence, Stress Response and Antibacterial Therapy

Yh¹,

Xl²

2017

J Antimicrob Agents

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Competence development for natural genetic transformation is widespread in bacteria, although it is a transient physiological state in which bacteria are capable of taking up and integrating exogenous DNA. Activation of competence enables the recipient bacteria to gain new genes, promoting the emergence of genetic variation, antibiotic resistance and evolution of virulence factors. It has been well studied that competence activation in bacteria requires one or more signal transduction pathways, many competence proteins and a complex regulatory network, which are finely controlled by a competence-specific master regulator. In the Genus Streptococcus, an alternative sigma factor, SigX coded by comX, is such a master regulator. The transcriptional activation of comX is the key step of competence induction in nearly all members of Streptococci. Although much is known of the regulatory cascade leading to competence induction, it was not until recently that a negative regulation of competence by a mechanism that involves regulated proteolysis of SigX has been recognized to play an important role in competence development in these bacteria. In particular, an adaptor protein MecA is found to target SigX for degradation by the proteases ClpC/ClpP, profoundly affecting the stability of SigX during competence development. Interestingly, SigX-mediated competence appears to be antagonistically connected with antibiotic-induced stress response by an unknown mechanism that involves activities of MecA and the Clp protease family. This discovery has added a new level of the complexity of competence regulatory network in Streptococci, leading to further investigation of such proteolytic regulation in competence, stress response, and antibacterial therapy.

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Microfluidic study of competence regulation in Streptococcus mutans: environmental inputs modulate bimodal and unimodal expression of comX

Cited by 99 publications

References 46 publications

Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans

Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans

MecA Protein Acts as a Negative Regulator of Genetic Competence in Streptococcus mutans

Proteolytic Regulation of Competence Development in the Genus Streptococcus: Implications in Competence, Stress Response and Antibacterial Therapy

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