The choline-binding proteins PspA, PspC, and LytA of Streptococcus pneumoniae and their interaction with human endothelial and red blood cells.
Cláudia VilhenaShanshan DuMiriana BattistaMartin WestermannThomas KohlerSven HammerschmidtPeter F ZipfelPublished in: Infection and immunity (2023)
Streptococcus pneumoniae is a Gram-positive opportunistic pathogen that can colonize the upper respiratory tract. It is a leading cause of a wide range of infectious diseases, including community-acquired pneumonia and meningitis. Pneumococcal infections cause 1-2 million deaths per year, most of which occur in developing countries. Here, we focused on three choline-binding proteins (CBPs), i.e., PspC, PspA, and LytA. These pneumococcal proteins have different surface-exposed regions but share related choline-binding anchors. These surface-exposed pneumococcal proteins are in direct contact with host cells and have diverse functions. We explored the role of the three CBPs on adhesion and pathogenicity in a human host by performing relevant imaging and functional analyses, such as electron microscopy, confocal laser scanning microscopy, and functional quantitative assays, targeting biofilm formation and the hemolytic capacity of S. pneumoniae . In vitro biofilm formation assays and electron microscopy experiments were used to examine the ability of knockout mutant strains lacking the lytA, pspC, or pspA genes to adhere to surfaces. We found that LytA plays an important role in robust synthesis of the biofilm matrix. PspA and PspC appeared crucial for the hemolytic effects of S. pneumoniae on human red blood cells. Furthermore, all knockout mutants caused less damage to endothelial cells than wild-type bacteria, highlighting the significance of each CPB for the overall pathogenicity of S. pneumoniae . Hence, in addition to their structural function within the cell wall of S. pneumoniae , each of these three surface-exposed CBPs controls or mediates multiple steps during bacterial pathogenesis.
Keyphrases
- biofilm formation
- endothelial cells
- electron microscopy
- candida albicans
- pseudomonas aeruginosa
- staphylococcus aureus
- respiratory tract
- escherichia coli
- wild type
- red blood cell
- high resolution
- high glucose
- infectious diseases
- cystic fibrosis
- community acquired pneumonia
- cell wall
- pluripotent stem cells
- high throughput
- induced apoptosis
- optical coherence tomography
- high speed
- oxidative stress
- cell proliferation
- transcription factor
- endoplasmic reticulum stress
- gram negative
- drug delivery
- vascular endothelial growth factor
- single cell
- single molecule
- cancer therapy
- cell death
- mass spectrometry
- binding protein
- signaling pathway
- label free
- cell migration