Streptococcus mutans suppresses filamentous growth of Candida albicans through secreting mutanocyclin, an unacylated tetramic acid
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ABSTRACT:
PROVIDER: PRJNA780563 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16951768.fastq.gz | Fastqsanger.gz | |||
| SRR16951768_1.fastq.gz | Fastqsanger.gz | |||
| SRR16951768_2.fastq.gz | Fastqsanger.gz | |||
| SRR16951769_1.fastq.gz | Fastqsanger.gz | |||
| SRR16951769_2.fastq.gz | Fastqsanger.gz |
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Project description:In this study, we discovered that S. mutans represses filamentous development and virulence in C. albicans through secreting a secondary metabolite, mutanocyclin (a tetramic acid).
2022-03-31 | GSE188886 | GEO
Project description:Polymicrobial biofilms are of large medical importance, but little is known about their physiology and the underlying interspecies interactions. Here we studied two human pathogens, the opportunistic fungus Candida albicans and the caries promoting bacterium Streptococcus mutans. Both species formed biofilms in monoculture, with C. albicans growing mainly in the virulence-associated hyphae form, and S. mutans forming a thick layer of extracellular polymeric substances (EPS). Biofilm growth was enhanced in dual-species biofilms, which reached twice the biomass of monospecies biofilms and higher cell numbers of both S. mutans and C. albicans. EPS production by S. mutans was strongly suppressed in dual-species biofilms. Virulence traits of S. mutans, e.g. genetic competence, biofilm formation and bacteriocin synthesis are controlled by quorum sensing through activation of the alternative sigma factor SigX. SigX is induced by the pheromones CSP (competence stimulating factor) or XIP (sigX inducing peptide). Strong induction of sigX was observed in dual species biofilms indicated by fluorescence of a reporter strain for the sigX promoter, S. mutans PcomX-gfp, as well as by qRT-PCR of comX. The peak of sigX expression occurred after 10 h of biofilm growth. Conditioned media from mixed biofilms but not from C. albicans or S. mutans cultivated alone activated sigX in the reporter strain. Deletion mutants for the comC and comS genes encoding the precursors of CSP and XIP, respectively, were constructed. Conditioned media from mixed biofilms with S. mutans DcomS were unable to induce sigX in the reporter strain, while deletion of comC had no effect. These data show that synthesis of XIP was induced in S. mutans by coculture with C. albicans. Transcriptome analysis of S. mutans in single and mixed biofilms confirmed strong induction of comS, sigX, and the downstream late competence genes in dual-species biofilms. Among the late competence genes, fratricins were discovered for the first time. The comCDE operon and bacteriocin related genes were also induced, but much weaker. Genes related to oxidative stress, chaperones and glycosyltransferase genes required for EPS synthesis from sucrose were down-regulated, while glycogen synthesis genes were up-regulated, indicating that S. mutans was protected from oxidative stress and provided with excess sugar for storage polymer synthesis in mixed biofilms. The data show that in dual-species biofilms, C. albicans improves growth of S. mutans, suppresses its EPS formation and induces the complete quorum sensing signalling system, thus fundamentally changing the virulence properties of the caries pathogen, including its potential interactions with other members of the polymicrobial dental plaque community.
2014-09-01 | GSE52543 | GEO
Project description:Streptococcus mutans and Candida albicans, as the most common bacterial and fungal in the oral cavity respectively, are considered as microbiological risk marker of early childhood caries. S. mutans MVs contain virulence proteins, which play a role in biofilm formation and disease progression. Our previous research found that S. mutans MVs harboring glucosyltransferases augment C. albicans biofilm formation through increasing the exopolysaccharide production, but the specific impact of S. mutans MVs on C. albicans virulence and pathogenicity is still unknown.
2022-05-31 | PXD034230 |
Project description:Polymicrobial biofilms are of large medical importance, but little is known about their physiology and the underlying interspecies interactions. Here we studied two human pathogens, the opportunistic fungus Candida albicans and the caries promoting bacterium Streptococcus mutans. Both species formed biofilms in monoculture, with C. albicans growing mainly in the virulence-associated hyphae form, and S. mutans forming a thick layer of extracellular polymeric substances (EPS). Biofilm growth was enhanced in dual-species biofilms, which reached twice the biomass of monospecies biofilms and higher cell numbers of both S. mutans and C. albicans. EPS production by S. mutans was strongly suppressed in dual-species biofilms. Virulence traits of S. mutans, e.g. genetic competence, biofilm formation and bacteriocin synthesis are controlled by quorum sensing through activation of the alternative sigma factor SigX. SigX is induced by the pheromones CSP (competence stimulating factor) or XIP (sigX inducing peptide). Strong induction of sigX was observed in dual species biofilms indicated by fluorescence of a reporter strain for the sigX promoter, S. mutans PcomX-gfp, as well as by qRT-PCR of comX. The peak of sigX expression occurred after 10 h of biofilm growth. Conditioned media from mixed biofilms but not from C. albicans or S. mutans cultivated alone activated sigX in the reporter strain. Deletion mutants for the comC and comS genes encoding the precursors of CSP and XIP, respectively, were constructed. Conditioned media from mixed biofilms with S. mutans DcomS were unable to induce sigX in the reporter strain, while deletion of comC had no effect. These data show that synthesis of XIP was induced in S. mutans by coculture with C. albicans. Transcriptome analysis of S. mutans in single and mixed biofilms confirmed strong induction of comS, sigX, and the downstream late competence genes in dual-species biofilms. Among the late competence genes, fratricins were discovered for the first time. The comCDE operon and bacteriocin related genes were also induced, but much weaker. Genes related to oxidative stress, chaperones and glycosyltransferase genes required for EPS synthesis from sucrose were down-regulated, while glycogen synthesis genes were up-regulated, indicating that S. mutans was protected from oxidative stress and provided with excess sugar for storage polymer synthesis in mixed biofilms. The data show that in dual-species biofilms, C. albicans improves growth of S. mutans, suppresses its EPS formation and induces the complete quorum sensing signalling system, thus fundamentally changing the virulence properties of the caries pathogen, including its potential interactions with other members of the polymicrobial dental plaque community. Dual-species biofilms of S. mutans and C. albicans and single-species biofilms of S. mutans were cultivated in 24-well microtitre plates in YNBB medium. Transcriptional profiles of S. mutans in single- and dual-species biofilms were analysed at early (6 h) and late (10 h) logarithmic phase of the biofilm growth, as well as after 24 h when biofilms entered stationary phase. Transcriptional profiles of S. mutans grown in the dual-species biofilms were compared to profiles obtained for single-species biofilm from the same time point. Three biological and one to two technical replicas were used in the microarray study. RNA samples were labeled with Cy3 or Cy5 using the ULS fluorescent labeling kit (Kreatech, Germany). Seven hundred nanograms of Cy3 or Cy5 labeled RNA after fragmentation were hybridized to the microarray at 65M-BM-0C for 17 h using the Agilent hybridization chamber according to the manufacturer's instructions. The arrays were scanned using the Agilent DNA microarray scanner and the raw data were extracted using Agilent Feature Extraction software (v. 10.7).
2014-09-01 | E-GEOD-52543 | biostudies-arrayexpress
Project description:Candida albicans is an opportunistic fungal pathogen capable of causing superficial and systemic infections in humans. The ability of C. albicans to switch between various morphological forms depending on its host environment is thought to contribute to its virulence. Filamentous growth states are associated with tissue invasion, biofilm formation, evasion of innate host defences and mating. Although the mechanisms of activation of filamentous growth pathways are well understood, less is known about which factors control the negative regulation of filamentation. In this study, we have identified a previously uncharacterized Orf that shares sequence similarity with Saccharomyces cerevisiae Dig1p and Dig2p. Deletion of the gene encoding this Orf triggers invasive growth in C. albicans and so we have retained the yeast designation of Dig1 (for Down-regulation of Invasive Growth). Mutants lacking CaDIG1 form cultures of hyperpolarized cells, form robust biofilms, are highly invasive in vitro but not in vivo and are constitutively activated for the pheromone response. Deletion of key transcription factors that act downstream of Dig1p provide evidence to suggest that CaDig1 regulates filamentation and mating through multiple signalling pathways.
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Project description:Candida albicans is an opportunistic fungal pathogen capable of causing superficial and systemic infections in humans. The ability of C. albicans to switch between various morphological forms depending on its host environment is thought to contribute to its virulence. Filamentous growth states are associated with tissue invasion, biofilm formation, evasion of innate host defences and mating. Although the mechanisms of activation of filamentous growth pathways are well understood, less is known about which factors control the negative regulation of filamentation. In this study, we have identified a previously uncharacterized Orf that shares sequence similarity with Saccharomyces cerevisiae Dig1p and Dig2p. Deletion of the gene encoding this Orf triggers invasive growth in C. albicans and so we have retained the yeast designation of Dig1 (for Down-regulation of Invasive Growth). Mutants lacking CaDIG1 form cultures of hyperpolarized cells, form robust biofilms, are highly invasive in vitro but not in vivo and are constitutively activated for the pheromone response. Deletion of key transcription factors that act downstream of Dig1p provide evidence to suggest that CaDig1 regulates filamentation and mating through multiple signalling pathways. Transcriptional analysis of the C. albicans dig1Δ/dig1Δ homozygous mutant versus the wild type (SN148) in the MTLa/alpha background. Four biological replicates of the mutant and the wild type were included in the analysis. Samples were grown at 30 °C in YPD medium plus uridine
2015-08-31 | E-GEOD-70085 | biostudies-arrayexpress
Project description:To investigate the function of Rfg1 in sensing acidic pH and regulating filamentation in C. albicans, we performed the global gene expression profile analysis of WT and rfg1/rfg1 mutant.We reveal that Rfg1 is an essential acidic pH sensor in C. albicans. Rfg1 regulates filamentous growth in acidic pH condition via co-regulation of Rim101-Phr1 pathway, cAMP signaling pathway,and the transcription factors Bcr1, Efg1, Flo8, and Hgc1.
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Project description:Skn7 is a conserved fungal heat shock factor-type transcriptional regulator. It participates in maintaining cell wall integrity and regulates the osmotic/oxidative stress response (OSR) in S. cerevisiae, where it is part of a two-component signal transduction system. Here, we comprehensively address the function of Skn7 in the human fungal pathogen Candida albicans. We provide evidence reinforcing functional divergence, with loss of the cell wall/osmotic stress-protective roles and acquisition of the ability to regulate morphogenesis on solid medium. Mapping of the Skn7 transcriptional circuitry, through combination of genome-wide expression and location technologies, pointed to a dual regulatory role encompassing OSR and filamentous growth. Genetic interaction analyses revealed close functional interactions between Skn7 and master regulators of morphogenesis, including Efg1, Cph1 and Ume6. Intracellular biochemical assays revealed that Skn7 is crucial for limiting the accumulation of reactive oxygen species (ROS) during filamentous growth on solid medium. Interestingly, functional domain mapping using site-directed mutagenesis allowed decoupling of Skn7 function in morphogenesis from protection against intracellular ROS. Our work identifies Skn7 as an integral part of the transcriptional circuitry controlling C. albicans filamentous growth and illuminates how C. albicans relies on an evolutionarily-conserved regulator to protect itself from intracellular ROS during morphological development.
2017-06-30 | GSE85275 | GEO