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| Status |
Public on Aug 21, 2017 |
| Title |
Pneumococci in the heart subvert the host response through biofilm-mediated macrophage killing |
| Organisms |
Mus musculus; Streptococcus pneumoniae TIGR4 |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
For over 130 years, invasive pneumococcal disease has been associated with the presence of extracellular diplococci or short chains in affected tissues. Herein, we show that Streptococcus pneumoniae that invade the myocardium from the bloodstream replicate within cellular vesicles and transition into non-purulent biofilms. Pneumococci within cardiac microlesions exhibited salient biofilm properties including intrinsic resistance to antibiotic killing and the presence of an extracellular matrix. Dual RNA-seq data generated from heart- and blood-isolated pneumococci confirmed the biofilm phenotype in vivo and revealed stark anatomical site-specific differences in virulence gene expression; the latter having major implications on vaccine antigen selection. Genes within three genomic islands were identified as exclusively expressed in vivo. Deletion of one such island, i.e. Region of Diversity 12, resulted in a biofilm-deficient and highly inflammogenic phenotype, suggesting a link between the ability to form biofilms and a dampened host-response. We subsequently determined that biofilm pneumococci subvert cytokine/chemokine production and myocardial neutrophil infiltration by rapidly killing cardiac macrophages in a pneumolysin dependent manner. Our findings contradict the emerging notion that biofilm pneumococci are immunoquiescent and instead show that biofilm S. pneumoniae actively suppress the host response through pneumolysin-mediated immune cell killing.
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| Overall design |
14 mRNA profiles of Streptococcus pneumoniae samples that were grown under different conditions were generated using deep sequencing (3 planktonic, 3 biofilm, 3 infected mouse hearts, 2 infected mouse blood and 3 uninfected mouse hearts).
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| Contributor(s) |
Shenoy AT, Gilley RP, Kumar N, Hinkle W, Gonzalez-Juarbe N, Wang Y, Brissac T, Daugherty SC, Shetty AC, Ott S, Tallon LJ, Deshane J, Tettelin H, Orihuela CJ |
| Citation(s) |
28841717 |
| Submission date |
Aug 26, 2016 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Suvarna Nadendla |
| Organization name |
University of Maryland School of Medicine
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| Department |
Institute for Genome Sciences
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| Street address |
670 W.Baltimore Street
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21201 |
| Country |
USA |
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| Platforms (2) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL22373 |
Illumina HiSeq 4000 (Streptococcus pneumoniae TIGR4) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA340293 |
| SRA |
SRP083088 |
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