In some individuals, an influenza A virus infection can cause asymptomatic Staphylococcus aureus (S. aureus) to travel to the lungs where it can trigger severe, sometimes deadly, secondary pneumonia. S. aureus is one of the most common causes of secondary bacterial pneumonia in cases of seasonal influenza. Just how the influenza virus causes asymptomatic S. aureus infection to transition to invasive disease, however, has been unclear. A new mouse model designed by scientists at the University at Buffalo, State University of New York is helping scientists put together the pieces of this puzzle.
Previously, researchers had been studying this phenomenon by introducing S. aureus directly into the lungs of animals and studying it from there, but this does not mimic the natural pathogenesis of infection. In the new model, investigators developed a method of placing S. aureus into the nasal cavities of mice. They then infected the animals with influenza A virus to see what would happen.
“This study performed by Ryan Reddinger, a senior doctoral student in my laboratory, demonstrated that influenza A virus infection leads to the dissemination of S. aureus from the nasal cavity into the lungs, resulting in the development of secondary bacterial pneumonia in these mice,” said Anthony Campagnari, PhD, principal study investigator and professor of microbiology/immunology and medicine at the University at Buffalo, State University of New York. He said the model is very relevant to the current physiologic state in humans, where individuals are colonized by S. aureus in the nares and subsequently acquire a viral infection.
“The fascinating thing about this model is when we colonize mice with S. aureus, it remains in the nares for up to 7 days without obvious signs of disease and does not appear to move to the lungs on its own. The bacteria only disseminates to the lungs in response to the subsequent viral infection,” said Dr. Campagnari.
It has been well known that when a person gets a viral infection, there are certain physiologic changes that occur in the nasopharynx that are related to damage of host cells and host response, including increased body temperature and release of ATP, glucose, and norepinephrine. With their model, the researchers discovered that a combination of these factors, in the absence of influenza A virus, will cause S. aureus to leave the nasopharynx and travel to the lungs.
Approximately 30% to 80% of the population are asymptomatically colonized with S. aureus, and this colonization state serves as a reservoir for invasive staphylococcal disease. The new model could lead to novel ways of treating or preventing secondary bacterial pneumonia, which is often severe, causing extensive damage to the respiratory tract including necrosis of lung tissue.
“This study has established a physiologically relevant model, so we can now more carefully investigate the actual events involved after colonization with S. aureus and identify the primary factors that can lead to secondary bacterial pneumonia,” said Dr. Campagnari. “We don’t know why the viral infection induces the bacteria to disseminate to the lung, but now we can evaluate potential mechanisms more closely because of this model.” The researchers say the mouse model could be adapted to study other virus-bacterial interactions that cause other diseases.
The research was described in a study published this week in mBio, an online open-access journal of the American Society for Microbiology.