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Title: Synergistic Activity of Mobile Genetic Element Defences in Streptococcus pneumoniae.
Authors: Kwun, Min Jung
Oggioni, Marco R.
Bentley, Stephen D.
Fraser, Christophe
Croucher, Nicholas J.
First Published: 13-Sep-2019
Publisher: MDPI
Citation: Genes 2019, 10(9), 707;
Abstract: A diverse set of mobile genetic elements (MGEs) transmit between Streptococcus pneumoniae cells, but many isolates remain uninfected. The best-characterised defences against horizontal transmission of MGEs are restriction-modification systems (RMSs), of which there are two phase-variable examples in S. pneumoniae. Additionally, the transformation machinery has been proposed to limit vertical transmission of chromosomally integrated MGEs. This work describes how these mechanisms can act in concert. Experimental data demonstrate RMS phase variation occurs at a sub-maximal rate. Simulations suggest this may be optimal if MGEs are sometimes vertically inherited, as it reduces the probability that an infected cell will switch between RMS variants while the MGE is invading the population, and thereby undermine the restriction barrier. Such vertically inherited MGEs can be deleted by transformation. The lack of between-strain transformation hotspots at known prophage att sites suggests transformation cannot remove an MGE from a strain in which it is fixed. However, simulations confirmed that transformation was nevertheless effective at preventing the spread of MGEs into a previously uninfected cell population, if a recombination barrier existed between co-colonising strains. Further simulations combining these effects of phase variable RMSs and transformation found they synergistically inhibited MGEs spreading, through limiting both vertical and horizontal transmission.
DOI Link: 10.3390/genes10090707
eISSN: 2073-4425
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: The following are available online at Figures S1: Vertical inheritance of mobile genetic elements in S. pneumoniae expressing different variants of the phase-variable SpnIV RMS, S2: Heatmap displaying the results of simulations in which a cellular population expressing a phase-variable RMS was repeatedly challenged by MV-type invading MGEs, S3: Heatmap showing the results of simulations of sequence exchange between a transformable S. pneumoniae population, initiated at carrying capacity , S4: Heatmap showing the results of simulations of sequence exchange between a transformable S. pneumoniae population, initiated at carrying capacity, repeatedly challenged by MGE invasions, S5: Heatmap showing the outputs of simulations of sequence exchange between a transformable S. pneumoniae population expressing a phase-variable RMS, with τ varying between variants, Table S1: Primers used to quantify variants of the tvr locus in S. pneumoniae RMV5 and RMV8. The updated C++ model code used for simulations is available from [73].
Appears in Collections:Published Articles, Dept. of Genetics

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