Streptococcus pneumoniae Serine Protease HtrA, but Not SFP or PrtA, Is a Major Virulence Factor in Pneumonia
Publication year
2013Source
PLoS One, 8, 11, (2013), article e80062ISSN
Publication type
Article / Letter to editor
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Organization
Laboratory of Genetic, Endocrine and Metabolic Diseases
Paediatrics - OUD tm 2017
CMBI
Journal title
PLoS One
Volume
vol. 8
Issue
iss. 11
Subject
IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism; N4i 1: Pathogenesis and modulation of inflammation NCMLS 1: Infection and autoimmunity; NCMLS 4: Energy and redox metabolismAbstract
Streptococcus (S.) pneumoniae is a common causative pathogen in pneumonia. Serine protease orthologs expressed by a variety of bacteria have been found of importance for virulence. Previous studies have identified two serine proteases in S. pneumoniae, HtrA (high-temperature requirement A) and PrtA (cell wall-associated serine protease A), that contributed to virulence in models of pneumonia and intraperitoneal infection respectively. We here sought to identify additional S. pneumoniae serine proteases and determine their role in virulence. The S. pneumoniae D39 genome contains five putative serine proteases, of which HtrA, Subtilase Family Protein (SFP) and PrtA were selected for insertional mutagenesis because they are predicted to be secreted and surface exposed. Mutant D39 strains lacking serine proteases were constructed by in-frame insertion deletion mutagenesis. Pneumonia was induced by intranasal infection of mice with wild-type or mutant D39. After high dose infection, only D39DeltahtrA showed reduced virulence, as reflected by strongly reduced bacterial loads, diminished dissemination and decreased lung inflammation. D39DeltaprtA induced significantly less lung inflammation together with smaller infiltrated lung surface, but without influencing bacterial loads. After low dose infection, D39DeltahtrA again showed strongly reduced bacterial loads; notably, pneumococcal burdens were also modestly lower in lungs after infection with D39Deltasfp. These data confirm the important role for HtrA in S. pneumoniae virulence. PrtA contributes to lung damage in high dose pneumonia; it does not however contribute to bacterial outgrowth in pneumococcal pneumonia. SFP may facilitate S. pneumoniae growth after low dose infection.
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- Academic publications [238441]
- Electronic publications [122541]
- Faculty of Medical Sciences [90373]
- Open Access publications [97533]
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