Anders P. Hakansson, PhD.

“We were asking, ‘What is the mechanism behind what makes us sick?’” says Anders P. Hakansson, PhD, pictured with first author and MD/PhD candidate Laura R. Marks.

UB Study Reveals How Colonizing Bacteria Become Virulent

Published September 26, 2013 This content is archived.

Story based on news release by Ellen Goldbaum

A University at Buffalo study has revealed how Streptococcus pneumoniae—bacteria that harmlessly colonize the mucous linings of human throats and noses—become virulent when they travel to the middle ears, lungs or bloodstream.

“When a viral infection comes in, there is this interkingdom signaling... If we can find ways to interrupt that signaling, we might be able to prevent disease. ”
Anders P. Hakansson, PhD
Assistant professor of microbiology and immunology

The study, featured as a research highlight in Nature, may lend insight into how the disease process can be thwarted.

Seeking Ways to Prevent Disease

“We are looking to find ways to interfere with the transition to disease,” says senior author Anders P. Hakansson, PhD, assistant professor of microbiology and immunology.

Few studies have examined the specific mechanism that makes S. pneumoniae suddenly leave the nose and travel into the lungs or middle ear where they cause disease, he says. “If we can understand that process, then maybe we can block it.”

Hakansson, whose lab is affiliated with the Witebsky Center for Microbial Pathogenesis and Immunology and the New York State Center of Excellence in Bioinformatics and Life Sciences, says the research demonstrates how the mammalian and bacterial kingdoms interact.

“Humans are the only natural hosts for these bacteria,” he explains. “When a viral infection comes in, there is this interkingdom signaling, where the bacteria respond to host molecules. If we can find ways to interrupt that signaling, we might be able to prevent disease.”

Findings Emphasize Host-Pathogen Interrelationships

The study underscores the importance of the interrelationship among the host, the pathogen and its co-colonizing neighbors, says first author Laura R. Marks, an MD/PhD student.

“One of the most exciting aspects of this research is that it really highlights how dynamic these organisms are,” she says.

“Disease doesn’t happen in a petri dish or culture tube; it happens in a complex microbial ecosystem that exists within the dynamic environment provided by the host,” she notes.

Growing Pneumococci, Triggering Its Travel

Hakansson and his colleagues previously found that the pneumococci form highly structured biofilm communities when they colonize the nose. “In their ‘default’ state, when these pathogens are living in biofilms, they have very little resemblance to the virulent bugs that make you ill,” Marks explains.

In this study, the research team grew these biofilms of pneumococci on top of human epithelial cells, where the bacteria normally grow. Next, they infected these bacteria with influenza A virus or exposed them to the conditions that typically accompany the flu, including: 

  • increased temperature that mimicked fever
  • increased concentrations of ATP, the energy molecule in cells
  • norepinephrine, the stress hormone released during flu infection

All three stimuli triggered a sudden release and departure of bacteria from the biofilm in the nose into areas such as the middle ears, lungs or bloodstream.

That’s when the disease process thrives.

“When the outside environment changes following influenza infection, the pathogens are able to take advantage of this state of decreased immunity by altering their outer shell, essentially arming themselves with the proteins that allow them to penetrate into normally sterile areas of the body and successfully evade our immune defenses,” says Marks.

Research Published in mBio

The research, funded by the Department of Microbiology and Immunology, has been published in mBio. The paper is entitled “Interkingdom Signaling Induces Streptococcus pneumoniae Biofilm Dispersion and Transition from Asymptomatic Colonization to Disease.”

Other co-authors are: