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Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
Published on: February 23, 2014
Identification of PblB mediating galactose-specific adhesion in a successful Streptococcus pneumoniae clone
Yu-Chia Hsieh1, Tzu-Lung Lin2, Che-Ming Lin1
1Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan.
Abstract:
The pneumococcal genome is variable and there are minimal data on the influence of the accessory genome on phenotype. Pneumococcal serotype 14 sequence type (ST) 46 had been the most prevalent clone causing pneumonia in children in Taiwan. A microarray was constructed using the genomic DNA of a clinical strain (NTUH-P15) of serotype 14 ST46. Using DNA hybridization, genomic variations in NTUH-P15 were compared to those of 3 control strains. Microarray analysis identified 7 genomic regions that had significant increases in hybridization signals in the NTUH-P15 strain compared to control strains. One of these regions encoded PblB, a phage-encoded virulence factor implicated (in Streptococcus mitis) in infective endocarditis. The isogenic pblB mutant decreased adherence to A549 human lung epithelial cell compared to wild-type NTUH-P15 strain (P = 0.01). Complementation with pblB restored the adherence. PblB is predicted to contain a galactose-binding domain-like region. Preincubation of NTUH-P15 with D-galactose resulted in decreases of adherence to A549 cell in a dose-dependent manner. Challenge of mice with NTUH-P15, isogenic pblB mutant and pblB complementation strains determined that PblB was required for bacterial persistence in the nasopharynx and lung. PblB, as an adhesin mediating the galactose-specific adhesion activity of pneumococci, promote pneumococcal clonal success.
Insights
Pneumococcal PblB protein enhances bacterial adherence to lung cells and is crucial for persistence in the respiratory tract. This adhesin promotes the success of pneumococcal clones, particularly in pediatric pneumonia cases.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- The pneumococcal genome exhibits variability, with limited understanding of accessory genome's phenotypic impact.
- Pneumococcal serotype 14 sequence type (ST) 46 was a predominant cause of pediatric pneumonia in Taiwan.
Purpose of the Study:
- To investigate genomic variations in a prevalent Taiwanese pneumococcal strain (serotype 14 ST46).
- To determine the role of the PblB protein in pneumococcal adherence and virulence.
Main Methods:
- Construction of a microarray using genomic DNA from a clinical pneumococcal strain (NTUH-P15).
- DNA hybridization to compare genomic variations against control strains.
- Analysis of a pblB mutant strain for adherence and in vivo persistence in a mouse model.
Main Results:
- Microarray identified 7 genomic regions with increased hybridization in NTUH-P15, including the PblB virulence factor.
- A pblB mutant showed significantly reduced adherence to human lung epithelial cells (A549).
- PblB was essential for bacterial persistence in the nasopharynx and lungs of mice.
Conclusions:
- PblB functions as a galactose-specific adhesin, mediating pneumococcal attachment to host cells.
- PblB contributes to the clonal success of Streptococcus pneumoniae by promoting adherence and persistence.
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