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Genes (Basel). 2019 Sep 13;10(9). pii: E707. doi: 10.3390/genes10090707.

Synergistic Activity of Mobile Genetic Element Defences in Streptococcus pneumoniae.

Author information

1
MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, St. Mary's Campus, Imperial College London, London W2 1PG, UK. min.kwun08@imperial.ac.uk.
2
Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK. mro5@leicester.ac.uk.
3
Pathogens and Microbes, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK. sdb@sanger.ac.uk.
4
Big Data Institute, Nuffield Department of Medicine, Old Road Campus, University of Oxford, Oxford OX3 7LF, UK. christophe.fraser@bdi.ox.ac.uk.
5
MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, St. Mary's Campus, Imperial College London, London W2 1PG, UK. n.croucher@imperial.ac.uk.

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.

KEYWORDS:

Streptococcus pneumoniae; mobile genetic elements; phase variation; pneumococcus; prophage; recombination; restriction-modification system; transformation

PMID:
31540216
PMCID:
PMC6771155
DOI:
10.3390/genes10090707
[Indexed for MEDLINE]
Free PMC Article

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