Transcriptome, Phenotypic, and Virulence Analysis of Streptococcus sanguinis SK36 Wild Type and Its CcpA-Null Derivative (ΔCcpA)
Catabolic control protein (CcpA) is linked to complex carbohydrate utilization and virulence factor in many bacteria species, influences the transcription of target genes by many mechanisms. To characterize the activity and regulatory mechanisms of CcpA in Streptococcus sanguinis, here, we analyzed...
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| Format: | Article |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2019.00411/full |
| _version_ | 1818959099927199744 |
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| author | Yibo Bai Mengmeng Shang Mengya Xu Anyi Wu Luning Sun Lanyan Zheng |
| author_facet | Yibo Bai Mengmeng Shang Mengya Xu Anyi Wu Luning Sun Lanyan Zheng |
| author_sort | Yibo Bai |
| collection | DOAJ |
| description | Catabolic control protein (CcpA) is linked to complex carbohydrate utilization and virulence factor in many bacteria species, influences the transcription of target genes by many mechanisms. To characterize the activity and regulatory mechanisms of CcpA in Streptococcus sanguinis, here, we analyzed the transcriptome of Streptococcus sanguinis SK36 and its CcpA-null derivative (ΔCcpA) using RNA-seq. Compared to the regulon of CcpA in SK36 in the RegPrecise database, we found that only minority of differentially expressed genes (DEGs) contained putative catabolite response element (cre) in their regulatory regions, indicating that many genes could have been affected indirectly by the loss of CcpA and analyzing the sequence of the promoter region using prediction tools is not a desirable method to recognize potential target genes of global regulator CcpA. Gene ontology and pathway analysis of DEGs revealed that CcpA exerts an influence predominantly involved in carbon catabolite metabolism and some amino acid catabolite pathways, which has been linked to expression of virulence genes in many pathogens and coordinately regulate the disease progression in vivo studies. However, in some scenarios, differences observed at the transcript level could not reflect the real differences at the protein level. Therefore, to confirm the differences in phenotype and virulence of SK36 and ΔCcpA, we characterized the role of CcpA in the regulation of biofilm development, EPS production and the virulence of Streptococcus sanguinis. Results showed CcpA inactivation impaired biofilm and EPS formation, and CcpA also involved in virulence in rabbit infective endocarditis model. These findings will undoubtedly contribute to investigate the mechanistic links between the global regulator CcpA and the virulence of Streptococcus sanguinis, further broaden our understanding of the relationship between basic metabolic processes and virulence. |
| first_indexed | 2024-12-20T11:36:16Z |
| format | Article |
| id | doaj.art-cecc17107b614300bee1bb2689334349 |
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| language | English |
| last_indexed | 2024-12-20T11:36:16Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-cecc17107b614300bee1bb26893343492022-12-21T19:42:07ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882019-12-01910.3389/fcimb.2019.00411485191Transcriptome, Phenotypic, and Virulence Analysis of Streptococcus sanguinis SK36 Wild Type and Its CcpA-Null Derivative (ΔCcpA)Yibo Bai0Mengmeng Shang1Mengya Xu2Anyi Wu3Luning Sun4Lanyan Zheng5Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Scientific Research, Peking Union Medical College Hospital (East), Beijing, ChinaDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, ChinaDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaCatabolic control protein (CcpA) is linked to complex carbohydrate utilization and virulence factor in many bacteria species, influences the transcription of target genes by many mechanisms. To characterize the activity and regulatory mechanisms of CcpA in Streptococcus sanguinis, here, we analyzed the transcriptome of Streptococcus sanguinis SK36 and its CcpA-null derivative (ΔCcpA) using RNA-seq. Compared to the regulon of CcpA in SK36 in the RegPrecise database, we found that only minority of differentially expressed genes (DEGs) contained putative catabolite response element (cre) in their regulatory regions, indicating that many genes could have been affected indirectly by the loss of CcpA and analyzing the sequence of the promoter region using prediction tools is not a desirable method to recognize potential target genes of global regulator CcpA. Gene ontology and pathway analysis of DEGs revealed that CcpA exerts an influence predominantly involved in carbon catabolite metabolism and some amino acid catabolite pathways, which has been linked to expression of virulence genes in many pathogens and coordinately regulate the disease progression in vivo studies. However, in some scenarios, differences observed at the transcript level could not reflect the real differences at the protein level. Therefore, to confirm the differences in phenotype and virulence of SK36 and ΔCcpA, we characterized the role of CcpA in the regulation of biofilm development, EPS production and the virulence of Streptococcus sanguinis. Results showed CcpA inactivation impaired biofilm and EPS formation, and CcpA also involved in virulence in rabbit infective endocarditis model. These findings will undoubtedly contribute to investigate the mechanistic links between the global regulator CcpA and the virulence of Streptococcus sanguinis, further broaden our understanding of the relationship between basic metabolic processes and virulence.https://www.frontiersin.org/article/10.3389/fcimb.2019.00411/fullCcpARNA-seqDEGsEPSbiofilmStreptococcus sanguinis |
| spellingShingle | Yibo Bai Mengmeng Shang Mengya Xu Anyi Wu Luning Sun Lanyan Zheng Transcriptome, Phenotypic, and Virulence Analysis of Streptococcus sanguinis SK36 Wild Type and Its CcpA-Null Derivative (ΔCcpA) Frontiers in Cellular and Infection Microbiology CcpA RNA-seq DEGs EPS biofilm Streptococcus sanguinis |
| title | Transcriptome, Phenotypic, and Virulence Analysis of Streptococcus sanguinis SK36 Wild Type and Its CcpA-Null Derivative (ΔCcpA) |
| title_full | Transcriptome, Phenotypic, and Virulence Analysis of Streptococcus sanguinis SK36 Wild Type and Its CcpA-Null Derivative (ΔCcpA) |
| title_fullStr | Transcriptome, Phenotypic, and Virulence Analysis of Streptococcus sanguinis SK36 Wild Type and Its CcpA-Null Derivative (ΔCcpA) |
| title_full_unstemmed | Transcriptome, Phenotypic, and Virulence Analysis of Streptococcus sanguinis SK36 Wild Type and Its CcpA-Null Derivative (ΔCcpA) |
| title_short | Transcriptome, Phenotypic, and Virulence Analysis of Streptococcus sanguinis SK36 Wild Type and Its CcpA-Null Derivative (ΔCcpA) |
| title_sort | transcriptome phenotypic and virulence analysis of streptococcus sanguinis sk36 wild type and its ccpa null derivative δccpa |
| topic | CcpA RNA-seq DEGs EPS biofilm Streptococcus sanguinis |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2019.00411/full |
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