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Synergistic Activity of Mobile Genetic Element Defences in Streptococcus pneumoniae.

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journal contribution
posted on 07.10.2019, 12:16 by Min Jung Kwun, Marco R. Oggioni, Stephen D. Bentley, Christophe Fraser, Nicholas J. Croucher
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.

Funding

This research was funded by the BBSRC, grant number BB/N002903/1. N.J.C. was supported by a Sir Henry Dale fellowship jointly funded by Wellcome and the Royal Society, grant number 104169/Z/14/Z. The APC was funded by Wellcome.

History

Citation

Genes 2019, 10(9), 707;

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Genetics and Genome Biology

Version

VoR (Version of Record)

Published in

Genes 2019

Publisher

MDPI

eissn

2073-4425

Acceptance date

06/09/2019

Copyright date

2019

Available date

07/10/2019

Publisher version

https://www.mdpi.com/2073-4425/10/9/707

Notes

The following are available online at http://www.mdpi.com/2073-4425/10/9/707/s1: 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].

Language

en