Targeted control of toxin production by a mobile genetic element in Streptococcus pneumoniae.

BioRxiv : the Preprint Server for Biology
Ruth C Massey

Abstract

Streptococcus pneumoniae is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated 800,000 deaths worldwide in those under five attributable to invasive pneumococcal disease each year. The cytolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, however, despite its importance to both the colonisation and pathogenic capabilities of this pathogen, the regulation of its expression is not well defined. Using a genome-wide association approach we identified over a hundred potential affectors of Ply activity, including the Integrative and Conjugative Element (ICE) ICESp23FST81. This regulatory effect is mediated through the activity of a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like nuclease domains. The ZomB protein has potent ATP-dependent nuclease activity and binds specifically to the DNA containing a BOX repeat region that forms part of the ply operon. We hypothesise that with over 100 BOX regions across the pneumococcal genome, the acquisition of the zomB gene on ICESp23FST81 has the potential to re-wire the transcriptional...Continue Reading

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