Published September 29, 2016
Their research, published in August in mBio, provides a new model for studying why the bacteria Staphylococcus aureus (S. aureus) can trigger severe, sometimes deadly secondary bacterial pneumonia in some people who are infected with influenza A virus.
“This study has established a physiologically relevant
model, so we can now more carefully evaluate the actual events
involved after colonization with S. aureus and identify the primary
factors that can lead to secondary bacterial pneumonia,” says
senior author Campagnari, who is also senior associate dean for
research and graduate education.
S. aureus is one of the most common causes of secondary bacterial pneumonia in cases of seasonal influenza and especially during influenza pandemics. Scientists have been studying this phenomenon by introducing S. aureus directly into the lungs of mice, but this does not mimic the natural pathogenesis of infection.
In the new model, Ryan Reddinger, a doctoral candidate in microbiology and immunology who is working in Campagnari’s lab, developed a technique where S. aureus stably colonizes the nares of mice that are then infected with influenza A virus, allowing researchers to follow the natural course of infection.
Reddinger’s work demonstrates 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 the mice.
“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,” Campagnari notes.
“The fascinating thing about this model is that when we
colonize mice with S. aureus, it remains in the nares for up to
seven 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.”
When someone has a viral infection, certain physiologic changes occur in the nasopharynx that are related to damage of host cells and host responses, including increased body temperature and release of glucose, norepinephrine and the cellular energy carrier adenosine triphosphate.
With their model, the UB 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.
The new model could lead to novel ways of treating or preventing secondary bacterial pneumonia, which is often severe and can cause extensive damage to the respiratory tract, including necrosis of lung tissue.
“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,” Campagnari says, adding that it could be adapted to study other virus-bacterial interactions.
Nicole R. Luke-Marshall, PhD, research assistant professor of microbiology and immunology, and Anders P. Hakansson, PhD, former assistant professor of microbiology and immunology, are additional study authors.