Scientists identify new pathogenic mechanisms of bacterial surface proteins responsible for pneumonia

Attacks of the flu virus can be difficult, but can be fatal if pneumococcus enters the mixture.

Researchers are now discovering additional reasons for the severity of this double infection by identifying new pathogenic mechanisms of bacterial surface proteins responsible for pneumonia. Streptococcus pneumoniae.. This insight comes more than 30 years after the discovery of a surface protein called Streptococcus pneumoniae surface protein A or PspA.

This new mechanism has been overlooked in the past because it promotes bacterial attachment to dead or dying lung epithelial cells rather than living cells. In the past, researchers typically used healthy lung cell monolayers to search for the bacterial adhesin that aids infection. Viral killing of lung cells in influenza Streptococcus pneumoniae Adhesion to the respiratory tract, thereby exacerbating illness and pneumonia.

Studies published in the journal Cell reportWas led by Dr. Carlos Orifela and Dr. David Briles, professors and emeritus professors of the Faculty of Microbiology, Birmingham, University of Alabama. Orihuela and Briles say their findings provide a detailed account of influenza A virus infection. Streptococcus pneumoniae Superinfection-Causes severe pneumonia and high mortality. This mechanism also shows the potential for treatment of illness and improved vaccination.

Historical example of influenza infection and subsequent fatal synergies Streptococcus pneumoniae Superinfection is found in lung samples that killed 40 to 50 million people in the 1918 Spanish flu pandemic. Most of these samples show coinfection or secondary infection. Streptococcus pneumoniae..

UAB studies on PspA began with scratching the head from an lung infection in mice with influenza A, followed by one of the wild-type. Streptococcus pneumoniae Has an intact PspA gene or variant Streptococcus pneumoniae It lacks PspA.Lung homogenates in wild-type infected mice had much higher numbers Streptococcus pneumoniae Bacteria rather than mutant-infected lungs.However, when researchers cleaned the inside of the lungs and collected their bronchoalveolar lavage fluid, they counted similar numbers of wild-type. Streptococcus pneumoniae And mutants.

“This unexpected result was interpreted to mean its wild type. Streptococcus pneumoniae Was more resistant to shedding Streptococcus pneumoniae There was a deletion in the pspA gene, which served as the basis for further experiments. “

From this clue, researchers were able to show that PspA acts as an adhesin to dying host cells, in addition to several other previously established pathogenic mechanisms. The researchers also elaborated on the molecular mechanism of this bacterial attachment.

Both influenza A infection and its release Streptococcus pneumoniae The toxin neumoricin causes the death of lung epithelial cells. When they are dying, the phosphatidylserine residues of the cell are inverted to the outer cell membrane, where they bind to the host enzyme glyceraldehyde-3-phosphate dehydrogenase, or GAPDH. In order, Streptococcus pneumoniae Bacterial surface PspA binds to GAPDH. Increased binding to lung cells via PspA-GAPDH Streptococcus pneumoniae Localization in the lower respiratory tract, which was enhanced by neumoricin exposure or co-infection with influenza A virus.

Studies with fragments of the PspA protein have shown that the 52 amino acid portion of the protein (amino acids 230-281) is required for GAPDH binding. When one of these binding fragments is injected into the lungs of influenza-infected mice, Streptococcus pneumoniae Probably a superinfection due to binding competition.

“Our findings support targeting the area of ​​PspA for treatment and vaccine development for influenza A /.Streptococcus pneumoniae “It’s important, and despite more than 30 years since its discovery, PspA has never been shown to function as an adhesin,” said Olivera. Therefore, the role of PspA in adherence. The discovery is Streptococcus pneumoniae With that host. “