Polyamine transporter in Streptococcus pneumoniae is essential for evading early innate immune responses in pneumococcal pneumonia
| Autor: | Aswathy N. Rai, Imran Sunesara, Justin A. Thornton, Edwin Swiatlo, Bindu Nanduri, John V. Stokes |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Neutrophils 030106 microbiology Virulence Biology medicine.disease_cause PTPRC Article Microbiology Mice 03 medical and health sciences Bacterial Proteins Operon Streptococcus pneumoniae Polyamines medicine Antigenic variation Animals Lung Immune Evasion Multidisciplinary Innate immune system Polyamine transport Wild type Biological Transport Pneumonia Pneumococcal medicine.disease Virology Immunity Innate 3. Good health DNA-Binding Proteins Mice Inbred C57BL Gene Expression Regulation Pneumococcal pneumonia biology.protein Cytokines Leukocyte Common Antigens Carrier Proteins Cell Adhesion Molecules Transcription Factors |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep26964 |
| Popis: | Streptococcus pneumoniae is the most common bacterial etiology of pneumococcal pneumonia in adults worldwide. Genomic plasticity, antibiotic resistance and extreme capsular antigenic variation complicates the design of effective therapeutic strategies. Polyamines are ubiquitous small cationic molecules necessary for full expression of pneumococcal virulence. Polyamine transport system is an attractive therapeutic target as it is highly conserved across pneumococcal serotypes. In this study, we compared an isogenic deletion strain of S. pneumoniae TIGR4 in polyamine transport operon (ΔpotABCD) with the wild type in a mouse model of pneumococcal pneumonia. Our results show that the wild type persists in mouse lung 24 h post infection while the mutant strain is cleared by host defense mechanisms. We show that intact potABCD is required for survival in the host by providing resistance to neutrophil killing. Comparative proteomics analysis of murine lungs infected with wild type and ΔpotABCD pneumococci identified expression of proteins that could confer protection to wild type strain and help establish infection. We identified ERM complex, PGLYRP1, PTPRC/CD45 and POSTN as new players in the pathogenesis of pneumococcal pneumonia. Additionally, we found that deficiency of polyamine transport leads to up regulation of the polyamine synthesis genes speE and cad in vitro. |
| Databáze: | OpenAIRE |
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