New model sheds light on secondary bacterial pneumonia

BUFFALO, N.Y. – For years, researchers have known that the bacteria Staphylococcus aureus (S. aureus) can trigger severe, sometimes deadly, secondary bacterial pneumonia in some people who are subsequently infected with influenza A virus, but scientists have not known exactly how this happens.

Now, University at Buffalo scientists have developed a new model for studying this phenomenon, which could lead to new ways to prevent secondary bacterial infections. The findings were published this week in mBio, an online open-access journal of the American Society for Microbiology.

“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,” said Anthony Campagnari, PhD, senior author and professor in the Department of Microbiology and Immunology and the Department of Medicine in the Jacobs School of Medicine and Biomedical Sciences at UB.

S. aureus is one of the most common causes of secondary bacterial pneumonia in cases of seasonal influenza. Scientists have been studying this phenomenon by introducing S. aureus directly into the lungs of mice. However, this does not mimic the natural pathogenesis of infection.

In the new model, Ryan Reddinger, a doctoral candidate in the UB Department of Microbiology and Immunology who is working in Campagnari’s lab, developed a technique where S. aureus stably colonizes the nares (nostrils) of mice and these animals are subsequently infected with influenza A virus to see what would happen.

“Ryan’s work 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 Campagnari. “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 seven days, without obvious signs of disease and does not appear to move to the lungs on its own,” Campagnari noted. “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 or ATP. 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.

“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,” said Campagnari. “In addition, this model could be adapted to study other virus-bacterial interactions.”

Founded in 1846, the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo is beginning a new chapter in its history with the largest medical education building under construction in the nation. The eight-story, 628,000-square-foot facility is scheduled to open in 2017. The new location puts superior medical education, clinical care and pioneering research in close proximity, anchoring Buffalo’s evolving comprehensive academic health center in a vibrant downtown setting. These new facilities will better enable the school to advance health and wellness across the life span for the people of New York and the world through research, clinical care and the education of tomorrow’s leaders in health care and biomedical sciences. The school’s faculty and residents provide care for the community’s diverse populations through strong clinical partnerships and the school’s practice plan, UBMD Physicians’ Group.