During the 1918 influenza pandemic, secondary bacterial pneumonia is believed to have caused more than 90% deaths, historic autopsy reports indicate. At present, nearly 30% adults hospitalized with viral community-acquired pneumonia develop bacterial co-infections.

Increasing antibiotic-resistance among bacteria, such as Staphylococcus aureus and Pseudomonas aeruginosa, that colonize our air passages and lead to lung infections is a continuous challenge in healthcare.

A new study sheds light on how primary viral infections may provoke secondary bacterial infections in our airways promising of new clinical strategies to thwart these dangerous and sometimes fatal microbial infections.

Tiny iron loaded extracellular vesicles (EVs) secreted by cells lining the host’s airways during a viral respiratory infection promote secondary bacterial growth, reports the new study led by scientists at the University of Pittsburgh.

These findings that provide a glimpse into how different kingdoms of microbes work together to undermine the host’s defense system, are published in an article titled “Extracellular vesicles promote transkingdom nutrient transfer during viral-bacterial co-Infection” in the journal Cell Reports. The study informs clinical therapeutic strategies that may be applied to curb secondary bacterial infections.

EVs that carry iron on their surface bound to a protein called transferrin, latch on to bacterial cells and supply them with growth-promoting essential nutrients. This results in the expansion of bacterial communities in the already-infected airways.

“The development of chronic bacterial infections often is preceded by acute viral infections, and such co-infections increase patients’ likelihood of death or lifelong disability,” says Jennifer Bomberger, PhD, associate professor in the Department of Microbiology & Molecular Genetics at Pittsburgh University and senior author on the study. “We wanted to understand what it is that the virus is doing that allows bacteria to get a foothold in the patient’s airways.”

University of Pittsburgh
Jennifer Bomberger, Ph.D., Associate professor in the Department of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine [University of Pittsburgh]

The scientists use a model of respiratory syncytial virus (RSV) and Pseudomonas aeruginosa co-infection to study the mechanism of viral-bacterial interactions in chronic lung disease. The severity of the co-infection depends on P. aeruginosa’s ability to form expansive communities of bacteria or biofilms, encased in a polymeric matrix.

Different cells in the body, including the flat cells that line our airways, constantly produce and expel tiny fluid-filled vesicles. It is a normal biological function. However, the authors in the current study show that the primary acute viral infection augments these normal biological processes manifold.

Moreover, the multitudes of tiny vesicles that are expelled into the airways, dock on the P. aeruginosa biofilms and promote their growth. The authors use fluorescent tags to monitor the EVs and measure bacterial growth curves using spectroscopic measures.

“Extracellular vesicles naturally occur in the body and are used by the organism as a communication tool,” says Bomberger. “It seems that bacteria co-opted this process for their own benefit.”

The authors report that the vesicles secreted by epithelial cells carry protein-bound iron on their surface, supplying bacteria with necessary nutrients to grow. The exact mechanism of how extracellular vesicles attach to bacteria remains to be investigated.

Matthew Hendricks, PhD, A lead author of the paper and former graduate student in Jennifer Bomberger’s laboratory [Source: Matthew Hendricks]

“It would be interesting to see the implications this mechanism has for the host’s immune response,” says Matthew Hendricks, PhD, a lead author of the paper and a former graduate student in Bomberger’s laboratory. “If extracellular vesicles can shield bacteria from the immune cells, that could decrease the host’s ability to detect the infection and help bacteria evade the immune response.”

Crosstalk between members of the viral and bacterial infectious communities results in poor bacterial clearance in patients suffering from acute and chronic lung disease. This study suggests a role of EVs during respiratory viral infections that facilitate trans-kingdom interactions and polymicrobial infections, providing a potential therapeutic target.

Since many infectious diseases are polymicrobial, and EVs are released by most cell types in the body, it is highly probable that such synergistic inter-microbial interactions occur in many other disease settings.