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

Tian, Xiaolin; Dong, Gaofeng; Liu, Tianlei; Gomez, Zubelda A.; Wahl, Astrid Klopstad; Hols, Pascal; Li, Yung-Hua

doi:10.1128/jb.00821-13

Cited by 38 publications

(71 citation statements)

References 46 publications

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“…Phenotypic characterization of an S. thermophilus clpC mutant revealed that ClpC plays a role in the development of genetic competence in this organism (310). The alternative sigma factor ComX, which drives the expression of competence genes, was shown in S. thermophilus and S. mutans to be under posttranslational regulation by ClpCP through active degradation (310)(311)(312)(313). This task is performed by ClpEP in S. pneumoniae (314).…”

Section: Treating Damaged Macromoleculesmentioning

confidence: 99%

Stress Physiology of Lactic Acid Bacteria

Papadimitriou

Alegría

Bron

et al. 2016

Microbiol Mol Biol Rev

539

404

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SUMMARYLactic acid bacteria (LAB) are important starter, commensal, or pathogenic microorganisms. The stress physiology of LAB has been studied in depth for over 2 decades, fueled mostly by the technological implications of LAB robustness in the food industry. Survival of probiotic LAB in the host and the potential relatedness of LAB virulence to their stress resilience have intensified interest in the field. Thus, a wealth of information concerning stress responses exists today for strains as diverse as starter (e.g.,Lactococcus lactis), probiotic (e.g., severalLactobacillusspp.), and pathogenic (e.g.,EnterococcusandStreptococcusspp.) LAB. Here we present the state of the art for LAB stress behavior. We describe the multitude of stresses that LAB are confronted with, and we present the experimental context used to study the stress responses of LAB, focusing on adaptation, habituation, and cross-protection as well as on self-induced multistress resistance in stationary phase, biofilms, and dormancy. We also consider stress responses at the population and single-cell levels. Subsequently, we concentrate on the stress defense mechanisms that have been reported to date, grouping them according to their direct participation in preserving cell energy, defending macromolecules, and protecting the cell envelope. Stress-induced responses of probiotic LAB and commensal/pathogenic LAB are highlighted separately due to the complexity of the peculiar multistress conditions to which these bacteria are subjected in their hosts. Induction of prophages under environmental stresses is then discussed. Finally, we present systems-based strategies to characterize the “stressome” of LAB and to engineer new food-related and probiotic LAB with improved stress tolerance.

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Section: Treating Damaged Macromoleculesmentioning

confidence: 99%

Stress Physiology of Lactic Acid Bacteria

Papadimitriou

Alegría

Bron

et al. 2016

Microbiol Mol Biol Rev

539

404

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“…Besides the transcriptional control of comX by the ComRS signaling system, the activity of X was also shown to be the target of a posttranslational negative control in one representative species of the pyogenic (25,29), salivarius (30,31), and mutans (32) groups. In these species, extensive in silico analyses did not allow the identification of a ComW homolog, suggesting that the regulatory system could be different from that in S. pneumoniae.…”

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confidence: 99%

“…In these species, extensive in silico analyses did not allow the identification of a ComW homolog, suggesting that the regulatory system could be different from that in S. pneumoniae. We and others have shown that the adaptor protein MecA and the ClpC ATPase subunit act as negative regulators of competence development in both S. thermophilus (30,31) and S. mutans (32). These studies revealed that the expression of late com genes and the abundance of X were increased in MecA-and ClpC-depleted strains compared to the isogenic wild-type (WT) strains (30)(31)(32) In addition, bacterial two-hybrid (B2H) assays suggested that MecA could interact in vivo with both X and ClpC (31,32).…”

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confidence: 99%

Control of Natural Transformation in Salivarius Streptococci through Specific Degradation of σ ^X by the MecA-ClpCP Protease Complex

et al. 2014

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cCompetence for natural DNA transformation is a tightly controlled developmental process in streptococci. In mutans and salivarius species, the abundance of the central competence regulator X is regulated at two levels: transcriptional, by the ComRS signaling system via the X /ComX/SigX-inducing peptide (XIP), and posttranscriptional, by the adaptor protein MecA and its associated Clp ATPase, ClpC. In this study, we further investigated the mechanism and function of the MecA-ClpC control system in the salivarius species Streptococcus thermophilus. Using in vitro approaches, we showed that MecA specifically interacts with both X and ClpC, suggesting the formation of a ternary X -MecA-ClpC complex. Moreover, we demonstrated that MecA ultimately targets X for its degradation by the ClpCP protease in an ATP-dependent manner. We also identify a short sequence (18 amino acids) in the N-terminal domain of X as essential for the interaction with MecA and subsequent X degradation. Finally, increased transformability of a MecA-deficient strain in the presence of subinducing XIP concentrations suggests that the MecA-ClpCP proteolytic complex acts as an additional locking device to prevent competence under inappropriate conditions. A model of the interplay between ComRS and MecA-ClpCP in the control of X activity is proposed.

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“…The low percentage of activation observed in the L. monocytogenes background (even with the overexpression of both regulators) suggests the existence of a strong negative regulation in the majority of the population. One candidate is the negative competence regulator MecA, which negatively regulates ComK in B. subtilis (42) and H in Streptococcus mutans and Streptococcus thermophilus (43,44). Further studies on H negative regulation are necessary to gain insight into the specific conditions that trigger the expression of competence genes.…”

Section: Discussionmentioning

confidence: 99%

Listeria monocytogenes σ^HContributes to Expression of Competence Genes and Intracellular Growth

Romero

Morikawa

2016

J Bacteriol

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The alternative sigma factor H has two functions in Gram-positive bacteria: it regulates sporulation and the development of genetic competence. Listeria monocytogenes is a nonsporulating species in which competence has not yet been detected. Nevertheless, the main competence regulators and a series of orthologous genes that form the competence machinery are present in its genome; some of the competence genes play a role in optimal phagosomal escape. In this study, strains overexpressing H and strains with a H deletion were used to elucidate the contribution of H to the expression of the competence machinery genes in L. monocytogenes. Gene expression analysis showed that H is, indeed, involved in comG and comE regulation. Unexpectedly, we observed a unique regulation scheme in which H and the transcription factor ComK were involved. Population-level analysis showed that even with the overexpression of both factors, only a fraction of the cells expressed the competence machinery genes. Although we could not detect competence, H was crucial for phagosomal escape, which implies that this alternative sigma factor has specifically evolved to regulate the L. monocytogenes intracellular life cycle. IMPORTANCEListeria monocytogenes can be an intracellular pathogen capable of causing serious infections in humans and animal species. Recently, the competence machinery genes were described as being necessary for optimal phagosomal escape, in which the transcription factor ComK plays an important role. On the other hand, our previous phylogenetic analysis suggested that the alternative sigma factor H might play a role in the regulation of competence genes. The present study shows that some of the competence genes belong to the H regulon and, importantly, that H is essential for intracellular growth, implying a unique physiological role of H among Firmicutes. Listeria monocytogenes is a Gram-positive foodborne pathogen with a multifaceted lifestyle: it can live harmlessly as a saprophyte in a diversity of environmental locations, but it can also be an intracellular pathogen capable of causing serious infections in humans and animal species. L. monocytogenes is a resilient microorganism: it cannot form spores, but it is able to endure several environmental and host stresses, such as low pH, low temperature, exposure to bile and fatty acids, high osmolarity, competition with intestinal flora, and intracellular nutrient and iron starvation (1, 2).Alternative sigma factors constitute the principal strategy used to control the response to specific stress conditions, growth transitions, and morphological changes by the regulation of stress response and virulence genes, other regulators, and small RNAs. L. monocytogenes has four alternative sigma factors:B , H , C , and L (3). Transcriptomic and proteomic analyses have found an overlap between the regulons and cross connections between regulators, suggesting a complex mechanism for the fine-tuning of stress responses in L. monocytogenes (4-6).B is the most extensively charact...

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

Cited by 38 publications

References 46 publications

Stress Physiology of Lactic Acid Bacteria

Stress Physiology of Lactic Acid Bacteria

Control of Natural Transformation in Salivarius Streptococci through Specific Degradation of σ ^X by the MecA-ClpCP Protease Complex

Listeria monocytogenes σ^HContributes to Expression of Competence Genes and Intracellular Growth

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

Cited by 38 publications

References 46 publications

Stress Physiology of Lactic Acid Bacteria

Stress Physiology of Lactic Acid Bacteria

Control of Natural Transformation in Salivarius Streptococci through Specific Degradation of σ X by the MecA-ClpCP Protease Complex

Listeria monocytogenes σHContributes to Expression of Competence Genes and Intracellular Growth

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Product

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Control of Natural Transformation in Salivarius Streptococci through Specific Degradation of σ ^X by the MecA-ClpCP Protease Complex

Listeria monocytogenes σ^HContributes to Expression of Competence Genes and Intracellular Growth