RT Journal Article SR Electronic(1) A1 Stevens, Emily J. A1 Morse, Daniel J. A1 Bonini, Dora A1 Duggan, Seána A1 Brignoli, Tarcisio A1 Recker, Mario A1 Lees, John A. A1 Croucher, Nicholas J. A1 Bentley, Stephen A1 Wilson, Daniel J. A1 Earle, Sarah G. A1 Dixon, Robert A1 Nobbs, Angela A1 Jenkinson, Howard A1 van Opijnen, Tim A1 Thibault, Derek A1 Wilkinson, Oliver J. A1 Dillingham, Mark S. A1 Carlile, Simon A1 McLoughlin, Rachel M. A1 Massey, Ruth C.YR 2022 T1 Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae JF Microbial Genomics, VO 8 IS 4 OP SP 000784 DO https://doi.org/10.1099/mgen.0.000784 PB Microbiology Society, SN 2057-5858, AB 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 3–4 million cases of severe disease and between 300 000 and 500 000 deaths attributable to pneumococcal disease each year. The haemolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion and transmission, the regulation of Ply production is not well defined. Using a genome-wide association approach, we identified a large number of potential affectors of Ply activity, including a gene acquired horizontally on the antibiotic resistance-conferring Integrative and Conjugative Element (ICE) ICESp23FST81. This gene encodes a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like domains with potent ATP-dependent nuclease activity. We found the regulatory effect of ZomB to be specific for the ply operon, potentially mediated by its high affinity for the BOX repeats encoded therein. Using a murine model of pneumococcal colonization, we further demonstrate that a ZomB mutant strain colonizes both the upper respiratory tract and lungs at higher levels when compared to the wild-type strain. While the antibiotic resistance-conferring aspects of ICESp23FST81 are often credited with contributing to the success of the S. pneumoniae lineages that acquire it, its ability to control the expression of a major virulence factor implicated in bacterial transmission is also likely to have played an important role., UL https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.000784