Six faces of Streptococcus

Like the faces of a die, Streptococcus pneumonia has six unique states it can switch to making it a leading cause of serious illness across the globe. A genetic switch which allows the bacterium – responsible for pneumonia, sinusitis, blood infections and meningitis – to change its characteristics into any of these six alternative states has now been discovered by an international team of researchers. Each form is randomly generated by a phase variable methylation system, as if the bacterium were playing dice and assigning themselves to any one of six potential outcomes. Some states favour invasive, life-threatening disease, while others a harmless colonisation or spread from person to person. “Facing a bacterial species with six or more phase variable systems is like being simultaneously confronted with six different bacteria,” said Professor Marco Oggioni from the University of Leicester. “It gives them an unfair advantage, but knowing the genetic basis now places us in an optimal position to reinvestigate drug and vaccine efficacy.” Using the latest DNA sequencing technology, researchers discovered that the underlying mechanism for such variation consists of genetic rearrangements in SpnD39III, a type 1 restriction-modification system. These rearrangements generate six alternative specificities with distinct methylation patterns. “We have shown that the pneumococcus generates subpopulations that have distinct DNA methylation patterns and we have shown that these epigenetic changes alter both gene expression patterns and virulence,” said Professor Michael Jennings from Griffith University. “Each time this bacterium divides it is like throwing a dice. Any one of six different cell types can appear. Understanding the role this six way switch plays in pneumococcal infections is key to understanding the disease and is crucial in the development of new and improved vaccines.” The work has been published in Nature Communications, and included researchers from the University of Adelaide and Pacific Biosciences. A random six-phase switch regulates pneumococcal virulence via global epigenetic changes