Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid
Streptococcus pneumoniae (pneumococcus) is a leading cause of severe invasive infectious diseases such as sepsis and meningitis. Understanding how pneumococcus adapts and survive in the human bloodstream environment and cerebrospinal fluid (CSF) is important for development of future treatment strat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1060583/full |
| _version_ | 1828162082171781120 |
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| author | Jens Sivkær Pettersen Frida Fabricius Høg Flemming Damgaard Nielsen Jakob Møller-Jensen Mikkel Girke Jørgensen |
| author_facet | Jens Sivkær Pettersen Frida Fabricius Høg Flemming Damgaard Nielsen Jakob Møller-Jensen Mikkel Girke Jørgensen |
| author_sort | Jens Sivkær Pettersen |
| collection | DOAJ |
| description | Streptococcus pneumoniae (pneumococcus) is a leading cause of severe invasive infectious diseases such as sepsis and meningitis. Understanding how pneumococcus adapts and survive in the human bloodstream environment and cerebrospinal fluid (CSF) is important for development of future treatment strategies. This study investigates the global transcriptional response of pneumococcus to human blood components and CSF acquired from discarded and anonymized patient samples. Extensive transcriptional changes to human blood components were observed during early stages of interaction. Plasma-specific responses were primarily related to metabolic components and include strong downregulation of fatty acid biosynthesis genes, and upregulation of nucleotide biosynthesis genes. No transcriptional responses specific to the active plasma proteins (e.g., complement proteins) were observed during early stages of interaction as demonstrated by a differential expression analysis between plasma and heat-inactivated plasma. The red blood cell (RBC)-specific response was far more complex, and included activation of the competence system, differential expression of several two-component systems, phosphotransferase systems and transition metal transporter genes. Interestingly, most of the changes observed for CSF were also observed for plasma. One of the few CSF-specific responses, not observed for plasma, was a strong downregulation of the iron acquisition system piuBCDA. Intriguingly, this transcriptomic analysis also uncovers significant differential expression of more than 20 small non-coding RNAs, most of them in response to RBCs, including small RNAs from uncharacterized type I toxin-antitoxin systems. In summary, this transcriptomic study identifies key pneumococcal metabolic pathways and regulatory genes involved with adaptation to human blood and CSF. Future studies should uncover the potential involvement of these factors with virulence in-vivo. |
| first_indexed | 2024-04-12T00:49:11Z |
| format | Article |
| id | doaj.art-6720bde402274dbc8b1055a7ad5fc7d1 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T00:49:11Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-6720bde402274dbc8b1055a7ad5fc7d12022-12-22T03:54:47ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-12-011310.3389/fmicb.2022.10605831060583Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluidJens Sivkær PettersenFrida Fabricius HøgFlemming Damgaard NielsenJakob Møller-JensenMikkel Girke JørgensenStreptococcus pneumoniae (pneumococcus) is a leading cause of severe invasive infectious diseases such as sepsis and meningitis. Understanding how pneumococcus adapts and survive in the human bloodstream environment and cerebrospinal fluid (CSF) is important for development of future treatment strategies. This study investigates the global transcriptional response of pneumococcus to human blood components and CSF acquired from discarded and anonymized patient samples. Extensive transcriptional changes to human blood components were observed during early stages of interaction. Plasma-specific responses were primarily related to metabolic components and include strong downregulation of fatty acid biosynthesis genes, and upregulation of nucleotide biosynthesis genes. No transcriptional responses specific to the active plasma proteins (e.g., complement proteins) were observed during early stages of interaction as demonstrated by a differential expression analysis between plasma and heat-inactivated plasma. The red blood cell (RBC)-specific response was far more complex, and included activation of the competence system, differential expression of several two-component systems, phosphotransferase systems and transition metal transporter genes. Interestingly, most of the changes observed for CSF were also observed for plasma. One of the few CSF-specific responses, not observed for plasma, was a strong downregulation of the iron acquisition system piuBCDA. Intriguingly, this transcriptomic analysis also uncovers significant differential expression of more than 20 small non-coding RNAs, most of them in response to RBCs, including small RNAs from uncharacterized type I toxin-antitoxin systems. In summary, this transcriptomic study identifies key pneumococcal metabolic pathways and regulatory genes involved with adaptation to human blood and CSF. Future studies should uncover the potential involvement of these factors with virulence in-vivo.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1060583/fullStreptococcus pneumoniae (pneumococcus)RNA-sequencinggene regulation and expressionsmall non-coding RNAshuman plasma and cerebrospinal fluidsepsis |
| spellingShingle | Jens Sivkær Pettersen Frida Fabricius Høg Flemming Damgaard Nielsen Jakob Møller-Jensen Mikkel Girke Jørgensen Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid Frontiers in Microbiology Streptococcus pneumoniae (pneumococcus) RNA-sequencing gene regulation and expression small non-coding RNAs human plasma and cerebrospinal fluid sepsis |
| title | Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid |
| title_full | Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid |
| title_fullStr | Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid |
| title_full_unstemmed | Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid |
| title_short | Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid |
| title_sort | global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid |
| topic | Streptococcus pneumoniae (pneumococcus) RNA-sequencing gene regulation and expression small non-coding RNAs human plasma and cerebrospinal fluid sepsis |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1060583/full |
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