Back to Search Start Over

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

Authors :
Emily J. Stevens
Daniel J. Morse
Dora Bonini
Seána Duggan
Tarcisio Brignoli
Mario Recker
John A. Lees
Nicholas J. Croucher
Stephen Bentley
Daniel J. Wilson
Sarah G. Earle
Robert Dixon
Angela Nobbs
Howard Jenkinson
Tim van Opijnen
Derek Thibault
Oliver J. Wilkinson
Mark S. Dillingham
Simon Carlile
Rachel M. McLoughlin
Ruth C. Massey
Source :
Stevens, E J, Morse, D J, Bonini, D, Duggan, S, Brignoli, T, Recker, M, Lees, J A, Croucher, N J, Bentley, S, Wilson, D J, Earle, S G, Dixon, R, Nobbs, A, Jenkinson, H, van Opijnen, T, Thibault, D, Wilkinson, O J, Dillingham, M S, Carlile, S, McLoughlin, R M & Massey, R C 2022, ' Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae ', Microbial Genomics, vol. 8, no. 4, 000784 . https://doi.org/10.1099/mgen.0.000784
Publication Year :
2022

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 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.

Details

Language :
English
Database :
OpenAIRE
Journal :
Stevens, E J, Morse, D J, Bonini, D, Duggan, S, Brignoli, T, Recker, M, Lees, J A, Croucher, N J, Bentley, S, Wilson, D J, Earle, S G, Dixon, R, Nobbs, A, Jenkinson, H, van Opijnen, T, Thibault, D, Wilkinson, O J, Dillingham, M S, Carlile, S, McLoughlin, R M & Massey, R C 2022, ' Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae ', Microbial Genomics, vol. 8, no. 4, 000784 . https://doi.org/10.1099/mgen.0.000784
Accession number :
edsair.doi.dedup.....eaa12bc3cf1377dff58940c9d98862f1
Full Text :
https://doi.org/10.1099/mgen.0.000784