World news – Iron-bearing extracellular vesicles are the key to viral-bacterial co-infection of the airways

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January 26, 2021

from the University of Pittsburgh

The mechanism by which acute respiratory viral infections promote secondary bacterial growth and respiratory infection depends on ferrous extracellular sacs secreted by the cells lining the host’s airways, researchers at the Faculty of Medicine report University of Pittsburgh in an article published today in Cell Reports.

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The sacs or « vesicles » that carry iron bound to a protein called transferrin attach to bacterial cells and provide them with essential nutrients, promoting the growth of expansive bacterial communities. The result gives us an insight into how bacteria exploit the host’s defense system against pathogens and offers a new opportunity to develop therapies to prevent secondary bacterial infections in a clinical setting.

« Chronic bacterial infections are often acute Viral infections precede, and such co-infections increase the likelihood of death or lifelong disability for patients, « said senior author Jennifer Bomberger, Ph.D., associate professor in the Department of Microbiology & Molecular Genetics at Pitt. « We wanted to understand what the virus is doing so that bacteria can gain a foothold in the patient’s airways. »

The prevention and control of secondary lung infections from increasingly antibiotic-resistant bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa remains a challenging problem in the healthcare sector. According to reviews of historical autopsy reports, more than 90% of deaths during the 1918 pandemic influenza are likely due to secondary bacterial pneumonia, and to date up to 30% of adults hospitalized with community-acquired pneumonia develop bacterial co-infections .

To investigate the mechanism of viral-bacterial interactions in chronic lung disease, the Pitt researchers used a model of Respiratory Syncytial Virus (RSV) and P. aeruginosa co-infection, the severity of which is dependent on the ability of P. aeruginosa depends to form biofilms. large communities of bacteria in a polymer matrix.

Using in vitro studies and fluorescence imaging, scientists have shown that the production and secretion of extracellular vesicles – two processes that occur routinely in different cell types in the body, including the respiratory epithelium – is promoted by an acute viral infection. It is crucial that these vesicles associate directly with P. aeruginosa biofilms and promote their growth. « Extracellular vesicles occur naturally in the body and are used by the organism as a means of communication, » said Bomberger. « It appears that bacteria have co-opted this process for their own benefit. »

While the exact mechanism by which extracellular vesicles attach to bacteria remains to be investigated, the researchers found that vesicles have protein-bound iron on their surface, as do bacteria with the necessary nutrients.

« It would be interesting to see what effect this mechanism has on the host’s immune response, » said Matthew Hendricks, Ph.D., lead author and former PhD student in Bomberger’s laboratory. « If extracellular vesicles can protect bacteria from immune cells, it could reduce the host’s ability to recognize the infection and help bacteria evade the immune response. »

It also appears that the mechanism of extracellular vesicle-dependent interaction between Viruses and bacteria is universal to different types of viruses, including other respiratory viruses and viruses that attack other mucosal sites such as the gastrointestinal tract.

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