Carnegie Mellon University
August 14, 2017

Bacterial Strains “Talk” to Each Other to Control Disease

Carnegie Mellon Researchers Have Identified Multiple Signals Pneumococcus Uses to Regulate Virulence

By Jocelyn Duffy

Researchers at Carnegie Mellon University have discovered two mechanisms that allow Streptococcus pneumoniae to communicate across cells and modulate the extent of human disease.

Streptococcus pneumoniae, frequently called pneumococcus, is one of the most common human pathogens. It causes diseases such as pneumonia, ear infections, sinus infections, blood stream infections and meningitis. Annually, pneumococcal infection causes an estimated one million deaths worldwide in children under the age of five.

While it can present as a major pathogen, pneumococcal infections are often asymptomatic. A community of pneumococcus can colonize the throat without causing any further symptoms. However, when these bacteria migrate to other tissues, they cause disease. The factors that direct the bacteria to switch from asymptomatic to symptomatic are poorly understood.

“Pneumococcus doesn’t usually cause disease but when it does it can be deadly,” said Carnegie Mellon Assistant Professor of Biological Sciences N. Luisa Hiller. “We need to figure out what the conversation is that causes the bacteria to say ‘let’s leave the throat and cause trouble.’”

Hiller studies the molecular mechanisms of pneumococcal disease. She is particularly interested in deciphering how bacteria communicate with each other and how this communication contributes to health or disease. 

Anagha Kadam, a Glen de Vries Presidential Fellow in the Department of Biological Sciences who works in Hiller’s lab, chose to look at one of the most drug-resistant lineages of pneumococcus, PMEN1. In a study published in PLoS Pathogens, Kadam focused on a region of the PMEN1 genome that is found in all PMEN1 strains but not in any other strains of pneumococcus.

Within this unique genomic region of PMEN1, the researchers found that there are  genes that code for a transcriptional regulator and a peptide. When the two are together, they send out a signal to neighboring PMEN1 cells, instructing them to produce a molecule that increases virulence.

The researchers also found out that this signal can be understood by other non-PMEN1 strains of pneumococcus, even though they do not code for either molecule. In other strains, this promiscuous PMEN1 signal controls a region of the genome that has also been implicated in disease.

Another recent discovery from the Hiller lab on bacterial communication, which is on the cover of Molecular Microbiology this week, describes a new pneumococcal peptide shared by all pneumococcal strains. Rolando Cuevas, a graduate student in the Hiller lab, discovered that this peptide signals pneumococcal cells to form larger communities and dramatically increases the extent of disease.

The researchers plan to continue to figure out the signals pneumococcus uses to communicate, and hope that once they have a more complete catalog, they can manipulate these signals to control the spread of disease.

Additional co-authors of these studies include Rory A. Eutsey, Xinyu Miao, Wenjie Xu, Carol A. Woolford, Jacob A. West-Roberts and Aaron P. Mitchell from Carnegie Mellon; Jason Rosch from St. Jude Children’s Research Hospital; Mark Longwell from the Allegheny Health Network; Todd Hillman from Allegheny General Hospital; Kevin M. Mason from Nationwide Children’s Hospital in Columbus; and Anfal Shakir Motib and Hasan Yesilkaya from the University of Leicester.

The research was funded by the National Institutes of Health (DC-011322).