Iron flecks feed ferocious infections
Viral infections in the respiratory system can have a nasty aftermath: On top of the illness they cause on their own, they are frequently followed by chronic bacterial infections—which are tough to stamp out and can even be deadly. Most people who died in the 1918 influenza pandemic actually succumbed to these secondary infections. Today, they are a scourge for people fighting off a variety of respiratory viruses, including influenza and even SARS-CoV-2.
Jennifer Bomberger, associate professor of microbiology and molecular genetics at Pitt, is beginning to unravel the biology at the root of this double whammy.
The new work stems from Bomberger’s long-term research on cystic fibrosis (CF), a genetic disease of the lungs (and other organs). Chronic bacterial lung infections are very detrimental to CF’s disease course, Bomberger says. “We don’t know how chronic bacterial infections in cystic fibrosis are established, but there are clinical observations that patients frequently develop a chronic bacterial infection around the same time they’ve had an acute respiratory viral infection.”
That observation led the team to ask the question: Does an acute viral infection change the environment of the respiratory tract to allow chronic bacterial infections to develop? That question has driven her lab’s research for a decade.
In 2016, they discovered a piece of the puzzle: For a bacterial infection to turn chronic, the bacteria must form what’s known as a biofilm, configuring themselves in a protective slime that is highly resistant to antibiotics. Working with human airway cells grown in a dish with the bacterium Pseudomonas aeruginosa, Bomberger and her colleagues found that several types of viral infections trigger biofilm formation in airway bacteria.
In the new work, published in Cell Reports in January, the researchers investigated how that might be happening.
They found that the bacteria are somehow obtaining iron, a nutrient that host cells typically sequester. A closer look revealed that the iron lies on the surface of tiny sacs, called extracellular vesicles, which host cells secrete—and that these sacs become more abundant when the cells are invaded by viruses.
“We discovered that these extracellular vesicles are released in higher numbers during an acute viral infection,” Bomberger says. “The bacteria are able to interact with these vesicles and acquire iron from them—and we think that’s actually what’s inducing biofilm growth.”
What these vesicles do normally, in the absence of infection, is still not fully understood. Current studies in Bomberger’s lab are trying to pin down what else they contain—but it’s undoubtedly not just iron, she says. For example, they may be carrying immune molecules meant to help fight the viral infection. Regardless, it appears that the bacteria may have somehow co-opted the host cells’ communication and delivery systems for their own voracious needs.
“The host antiviral response is really good at controlling the viral infection,” she says. “But it’s probably leaving an Achilles heel that the bacteria are exploiting,” which suggests some intriguing treatment implications. For example: combining antibiotics with iron chelation therapy could slough off the bacteria’s food supply. Potentially, that could help stave off such secondary infections—by turning feast to famine.