The CovR environmental sensor orchestrates competence bimodality in salivarius streptococci
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ABSTRACT:
PROVIDER: PRJNA665491 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12705300.fastq.gz | Fastqsanger.gz | |||
| SRR12705301.fastq.gz | Fastqsanger.gz | |||
| SRR12705299.fastq.gz | Fastqsanger.gz |
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Project description:In bacteria, phenotypic heterogeneity rescues the need for diversity in isogenic populations and allow concomitant multiple survival strategies when choosing only one is too risky. This powerful tactic is exploited for competence in streptococci and results in a bimodal activation, where only a subset of the community triggers the system. Deciphering the mechanisms underlying this puzzling behavior has remained challenging, especially since its study has been mainly achieved in S. mutans, where two different but interconnected regulation networks control competence. In this work, we sought to determine the origin of bimodality associated to the ComRS system thanks to the simplified S. salivarius model that harbors no supplemental signaling system. Using a single cell fluorescence reporter system together with the overexpression of the main actors of the regulation network, we showed that the ComR intracellular concentration is directly linked to the proportion of competent cells in the population. We report that this type of activation requires a functional positive feedback loop acting on comS through Opp and a putative ComS exporter, PptAB. To determine the origin of the heterogeneity amplified by the loop, we developed a mathematical model suggesting that either noise on ComS or ComR abundance could explain bimodality. Because ComR abundance is central for competence bimodal activation, we conducted an in silico identification and a systematic deletion of all the Two Component Systems (TCS) present in S. salivarius and identified CovRS, a well described virulence regulator in GAS and GBS, as a repressor of comR transcription. In vitro direct binding of CovR with the promoter of comR and transcriptomics confirmed those data. As CovRS integrates environmental stimuli that control ComR intracellular concentration, it represents the missing puzzle piece bridging environmental conditions and competence (bimodal) activation in salivarius streptococci.
2021-01-31 | GSE158512 | GEO
Project description:Small distortions in transcriptional networks might lead to drastic phenotypical changes, especially in cellular developmental programs such as competence for natural transformation. Here, we report a pervasive circuitry rewiring for competence and predation interplay in commensal streptococci. Canonically, in model species of streptococci such as Streptococcus pneumoniae and Streptococcus mutans, the pheromone-based two-component system BlpRH is a central node that orchestrates the production of antimicrobial compounds (bacteriocins) and incorporates signal from the competence activation cascade. However, the human commensal Streptococcus salivarius does not contain a functional BlpRH pair and in this species, the competence signaling system ComRS directly couples bacteriocin production and competence commitment. This network shortcut might account for an optimal reaction against microbial competitors and could explain the high prevalence of S. salivarius in the human digestive tract. Moreover, the broad spectrum of bacteriocin activity against pathogenic bacteria showcases the commensal and genetically tractable S. salivarius species as a user-friendly model for natural transformation and bacterial predation.
2018-01-10 | GSE100416 | GEO
Project description:The human oral cavity is one of the most competing environments, considering the extent and diversity of the bacterial community that colonizes it, as well as the multiple stresses to which it is subjected. The commensal species Streptococcus salivarius is one of the first colonizers of the oral mucosa (tongue, gums, inner cheeks and tooth enamel) in infants and remains predominant throughout the life of an adult. In order to adapt to diverse and variable environmental conditions, S. salivarius triggers in a coordinated way two bacterial developmental processes: competence (acquisition of extracellular DNA and new genetic traits) and predation (secretion of cytotoxic molecule), via ComR, a transcription factor activatable by a "pheromone" peptide. Nevertheless, the activation of other transcriptional regulators can uncouple these 2 mechanisms to allow, for example, only the production of toxins without triggering the competence phase.
2019-08-19 | GSE120640 | GEO
Project description:Synchronizing production of antibacterial compounds and integration of DNA released by dead cells, competence is one of the most efficient bacterial evolutionary and adaptative strategies. In most streptococci, this tactic is orchestrated by the ComRS system, a pheromone communication device providing competence bimodal initiation and sharp time window of activation. Understanding how this developmental process integrates multiple inputs to fine-tune the adequate response is a long-standing question. Actually, essential genes involved in the regulation of ComRS have been challenging to study. In this work, we built a conditional mutant library using the CRISPR-interference technology and developed three complementary screens to investigate competence genetic regulation in the human commensal Streptococus salivarius. We highlighted that competence increases upon cell-wall impairment, suggesting a connection between cell envelope stress and competence activation. Notably, we report the key role played by StkP, a serine-threonine kinase known to regulate cell-wall assembly. We showed that StkP controls competence by a mechanism responding to peptidoglycan fragments. Together, those data suggest a key cell-wall sensing mechanism coupling competence to cell envelope integrity.
2022-08-25 | GSE204976 | GEO
Project description:Molecular singularities in a pheromone sensor triumvirate desynchronize the competence-predation interplay in the human commensal Streptococcus salivarius
| PRJNA493819 | ENA
Project description: Not available
| S-EPMC8725580 | biostudies-literature
Project description: Not available
| S-EPMC9173638 | biostudies-literature
Project description:Streptococcus sanguinis is a major component of the oral flora and an important cause of infective endocarditis. The genome sequence of S. sanguinis strain SK36 was recently determined. A number of foreign genes acquired by natural transformation were detected, as well as orthologs of competence genes previously identified in other species. However, significant differences in the S. sanguinis competence system relative to that of other streptococci were noted. We sought to examine S. sanguinis genetic competence, to characterize the global transcriptional response to competence induction, and to compare our results with those obtained from previous analyses of other streptococci. A mutant possessing an in-frame deletion in the comC gene encoding the competence-stimulating peptide was created and confirmed to have the expected phenotype. Studies indicated that competence could be induced in this strain by addition of competence-stimulating peptide, and determined the optimal conditions to employ for this purpose. Expression was monitored by microarray analysis at multiple time points from 2.5 to 30 min after induction. Over 200 genes were identified whose expression was altered at least two-fold in at least one time point, with the majority upregulated. The M-bM-^@M-^\lateM-bM-^@M-^] response was typical of that seen in previous studies. However, comparison of the M-bM-^@M-^\earlyM-bM-^@M-^] response in S. sanguinis with that of other streptococci revealed unexpected heterogeneity with regard to the number of genes induced, the nature of these genes, and their putative upstream regulatory sequences. S. sanguinis possesses a comparatively limited early response, which may define a minimal competence regulatory circuit. Transcriptional analysis of S. sanguinis strain JFP41 cells 0 to 30 min after treatment with CSP. Biological replicates: 3 replicates each independently grown and harvested. 4 technical replicates per array
2011-01-21 | E-GEOD-21619 | biostudies-arrayexpress
Project description:Streptococcus sanguinis is a major component of the oral flora and an important cause of infective endocarditis. The genome sequence of S. sanguinis strain SK36 was recently determined. A number of foreign genes acquired by natural transformation were detected, as well as orthologs of competence genes previously identified in other species. However, significant differences in the S. sanguinis competence system relative to that of other streptococci were noted. We sought to examine S. sanguinis genetic competence, to characterize the global transcriptional response to competence induction, and to compare our results with those obtained from previous analyses of other streptococci. A mutant possessing an in-frame deletion in the comC gene encoding the competence-stimulating peptide was created and confirmed to have the expected phenotype. Studies indicated that competence could be induced in this strain by addition of competence-stimulating peptide, and determined the optimal conditions to employ for this purpose. Expression was monitored by microarray analysis at multiple time points from 2.5 to 30 min after induction. Over 200 genes were identified whose expression was altered at least two-fold in at least one time point, with the majority upregulated. The “late” response was typical of that seen in previous studies. However, comparison of the “early” response in S. sanguinis with that of other streptococci revealed unexpected heterogeneity with regard to the number of genes induced, the nature of these genes, and their putative upstream regulatory sequences. S. sanguinis possesses a comparatively limited early response, which may define a minimal competence regulatory circuit.
2011-01-21 | GSE21619 | GEO
Project description:Two covR mutant derivatives of parental strain MGAS2221 were recovered from mice experimentally infected with MGAS2221 and shown to differ in terms of the number and concentration of secreted proteins. One of the covR mutant strains had a secretion phenotype identical to a covS mutant strain, while the other had a secretion phenotype identical to a constructed covR mutant strain. To further investigate the potential differences between the two covR mutant strains we performed expression microarray analysis.
2009-06-06 | GSE16436 | GEO