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RSV increases the virulence of Streptococcus pneumoniae by binding to PBP1a: a new paradigm respiratory infection

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Streptococcus pneumoniae D39

SUBMITTER: Sulman Shafeeq

PROVIDER: E-GEOD-58427 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Respiratory syncytial virus increases the virulence of Streptococcus pneumoniae by binding to penicillin binding protein 1a. A new paradigm in respiratory infection.

Smith Claire M CM Sandrini Sara S Datta Sumit S Freestone Primrose P Shafeeq Sulman S Radhakrishnan Priya P Williams Gwyneth G Glenn Sarah M SM Kuipers Oscar P OP Hirst Robert A RA Easton Andrew J AJ Andrew Peter W PW O'Callaghan Christopher C

American journal of respiratory and critical care medicine 20140701 2

<h4>Rationale</h4>Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Coinfection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear.<h4>Objectives</h4>To determine if interaction between RSV and pneumococci enhances pneumococcal virulence.<h4>Methods</h4>We used confocal microscopy and Western blot to identify the receptors involved in direct binding of RSV and pneumococci, t ...[more]

PMID: 24941423

Similar Datasets

RSV vs BSA

Project description:Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Co-infection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72h and then challenged with pneumococci. Pneumococci were collected after 2h exposure and changes in gene expression determined using qRT-PCR. Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant upregulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is due to RSV G glycoprotein binding penicillin binding protein 1a. Conclusion: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection. Comparison of the Streptococcus pneumoniae D39 RSV treated compared to BSA Treated in BEBM medium One condition design comparision of two strains including a dye swap

2014-06-21 | E-GEOD-58425 | biostudies-arrayexpress

Protein P Vs Protein G

Project description:Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Co-infection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72h and then challenged with pneumococci. Pneumococci were collected after 2h exposure and changes in gene expression determined using qRT-PCR. Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant upregulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is due to RSV G glycoprotein binding penicillin binding protein 1a. Conclusion: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection. Comparison of the Streptococcus pneumoniae D39 Protein P treated compared to Protein GTreated in BEBM medium One condition design comparision of two strains including a dye swap

2014-06-21 | E-GEOD-58424 | biostudies-arrayexpress

Ascorbic acid-dependent gene expression in Streptococcus pneumoniae: the role of ascorbic acid in zinc starvation and the activator function of the transcriptional regulator UlaR2

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-01-21 | E-GEOD-64107 | biostudies-arrayexpress

Comparison of the Streptococcus pneumoniae D39 ulaR Mutant compared to D39 wild-type

Project description:Comparison of the Streptococcus pneumoniae D39 ulaR mutant compared to D39 wild type in M17 medium + 10mM ascorbic acid (AM17) One condition design comparision of two strains including a dye swap

2014-10-28 | E-GEOD-61649 | biostudies-arrayexpress

Comparison of the Streptococcus pneumoniae D39 grown in AM17 compared to D39 wild-type grown in M17

Project description:In this study, we have explored the impact of ascorbic acid on the transcriptome of Streptococcus pneumoniae D39. The expression of several genes and operons, including the ula operon (which has been previously shown to be involved in ascorbic acid utilization), the AdcR regulon (which has been previously shown to be involved in zinc transport and virulence) and a PTS operon (which we denote here as ula2 operon) were altered in the presence of ascorbic acid. The ula2 operon consists of five genes, including the transcriptional activator ulaR2. Our M-NM-2-galactosidase assay data and transcriptome comparison of the ulaR2 mutant with the wild-type demonstrated that the transcriptional activator UlaR2 in the presence of ascorbic acid activates the expression of the ula2 operon. We further predict a 16-bp regulatory site (5M-bM-^@M-^Y-ATATTGTGCTCAAATA-3M-bM-^@M-^Y) for UlaR2 binding in the Pula2. Furthermore, we have explored the effect of ascorbic acid on the expression of the AdcR regulon. Our ICP-MS analysis showed that addition of ascorbic acid to the medium causes zinc starvation in the cell that leads to the activation of the AdcR regulon. Comparison of the Streptococcus pneumoniae D39 compared to D39 wild type in M17 medium+ 10mM ascorbic acid (AM17) Two conditions design comparision of one strain including a dye swap

2015-01-21 | E-GEOD-64105 | biostudies-arrayexpress

Comparison of the Streptococcus pneumoniae D39 ulaR2 Mutant compared to D39 wild-type

Project description:In this study, we have explored the impact of ascorbic acid on the transcriptome of Streptococcus pneumoniae D39. The expression of several genes and operons, including the ula operon (which has been previously shown to be involved in ascorbic acid utilization), the AdcR regulon (which has been previously shown to be involved in zinc transport and virulence) and a PTS operon (which we denote here as ula2 operon) were altered in the presence of ascorbic acid. The ula2 operon consists of five genes, including the transcriptional activator ulaR2. Our M-NM-2-galactosidase assay data and transcriptome comparison of the ulaR2 mutant with the wild-type demonstrated that the transcriptional activator UlaR2 in the presence of ascorbic acid activates the expression of the ula2 operon. We further predict a 16-bp regulatory site (5M-bM-^@M-^Y-ATATTGTGCTCAAATA-3M-bM-^@M-^Y) for UlaR2 binding in the Pula2. Furthermore, we have explored the effect of ascorbic acid on the expression of the AdcR regulon. Our ICP-MS analysis showed that addition of ascorbic acid to the medium causes zinc starvation in the cell that leads to the activation of the AdcR regulon. Comparison of the Streptococcus pneumoniae D39 ulaR2 mutant compared to D39 wild type in M17 medium+ 10mM ascorbic acid (AM17) One condition design comparision of two strains including a dye swap

2015-01-21 | E-GEOD-64106 | biostudies-arrayexpress

Transcriptome comparison of rokA mutant to wild-type in the Streptococcus pneumoniae D39.

Project description:The Gram-positive human pathogen Streptococcus pneumoniae possesses an unusually high number of gene clusters specific for carbohydrate utilization. This provides it with the ability to use a wide array of sugars, which may aid during infection and survival in different environmental conditions present in the host. In this study, the regulatory mechanism of transcription of a gene cluster, SPD0424-28, putatively encoding a cellobiose/lactose-specific PTS, is investigated. Upstream of SPD0424 a gene was identified encoding a ROK-family transcriptional regulator (RokA: SPD0423). DNA microarray and transcriptional reporter analyses with a rokA mutant revealed that RokA acts as a transcriptional repressor of the SPD0424-28 operon. In conclusion, we have characterized the role of RokA on gene expression of S. pneumoniae. One condition design comparision of two strains including a dye swap

2012-10-22 | E-GEOD-41448 | biostudies-arrayexpress

Transcriptional and metabolic effects of glucose on S. pneumoniae sugar metabolism

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-09-01 | E-GEOD-70648 | biostudies-arrayexpress

Comparison of the Streptococcus pneumoniae D39 wild-type to the D39 galR mutant [GalM17]

Project description:We explored the regulatory mechanism of Leloir pathway genes in Streptococcus pneumoniae D39. Here, we demonstrate that the expression of galKT is galactose dependent. By microarray analysis and quantitative RT-PCR, we further show the role of the transcriptional regulator GalR, present upstream of galKT, as a transcriptional activator of galKT in the presence of galactose. Moreover, we predict a 19-bp regulatory site (5'-GATAGTTTAGTAAAATTTT-3' ) for the transcriptional regulator GalR in the promoter region of galK, which is also highly conserved in other streptococci. Growth comparison of Î galK with the D39 wildtype strain grown in the presence of galactose shows that galK is required for the proper growth of S. pneumoniae on galactose. Comparison of the Streptococcus pneumoniae D39 galR mutant compared to D39 wild type in M17 medium+ 0.5% (w/v) galactose (GalM17). One condition design comparison of two strains including a dye swap.

2015-10-30 | E-GEOD-74501 | biostudies-arrayexpress

Comparison of the Streptococcus pneumoniae D39 wild-type to the D39 galR mutant [GM17]

Project description:We explored the regulatory mechanism of Leloir pathway genes in Streptococcus pneumoniae D39. Here, we demonstrate that the expression of galKT is galactose dependent. By microarray analysis and quantitative RT-PCR, we further show the role of the transcriptional regulator GalR, present upstream of galKT, as a transcriptional activator of galKT in the presence of galactose. Moreover, we predict a 19-bp regulatory site (5'-GATAGTTTAGTAAAATTTT-3' ) for the transcriptional regulator GalR in the promoter region of galK, which is also highly conserved in other streptococci. Growth comparison of Î galK with the D39 wildtype strain grown in the presence of galactose shows that galK is required for the proper growth of S. pneumoniae on galactose. Comparison of the Streptococcus pneumoniae D39 galR mutant compared to D39 wild type in M17 medium+ 0.5% (w/v) glucose (GM17). One condition design comparison of two strains including a dye swap.

2015-10-30 | E-GEOD-74500 | biostudies-arrayexpress

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