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.
Highlights
Streptococcus pneumoniae is a genetically diverse gram-positive bacterial commensal and respiratory pathogen that can be divided into hundreds of distinct strains [1,2]
As restriction-modification systems (RMSs) inhibit the transmission of mobile genetic elements (MGEs) when they have discordant activities in source and
A naïve expectation would be that they operate most effectively when all variants are lytic S. pneumoniae phage have proved difficult to isolate [44], lysogenic or temperate phage have been readily identified from prophages in genomic data [5,45,46]
Summary
Streptococcus pneumoniae is a genetically diverse gram-positive bacterial commensal and respiratory pathogen that can be divided into hundreds of distinct strains [1,2]. The species can be commonly isolated from the nasopharynx of infants, typically occurring at prevalences of 20–90% [3]. Co-colonisation between distinct strains is common [4], facilitating the exchange of genetic variation through three primary recombination mechanisms. Two are driven by mobile genetic elements (MGEs): both phage and phage-related chromosomal islands move between S. pneumoniae cells in virion particles [5,6], whereas integrative and conjugative elements transmit via conjugative pili [7]. An immense diversity of these pneumococcal MGEs has been uncovered by genomic datasets [5,8].
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