A genomic view of experimental intra- and interspecies transformation of a rifampicin resistance allele into Neisseria meningitidis
Alfsnes, Kristian; Frye, Stephan Alfons; Eriksson, JE; Tonjum, Tone; Eldholm, Vegard; Brynildsrud, Ola Brønstad; Bohlin, Jon; Harrison, OB; Hood, D; Maiden, Martin C.J.; Ambur, Ole Herman
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2018-09-25Metadata
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Alfsnes k, Frye SA, Eriksson, Tonjum T, Eldholm V, Brynildsrud OB, Bohlin J, Harrison O, Hood D, Maiden MC, Ambur OH. A genomic view of experimental intra- and interspecies transformation of a rifampicin resistance allele into Neisseria meningitidis. Microbial Genomics. 2018 http://dx.doi.org/10.1099/mgen.0.000222Abstract
The spread of antibiotic resistance within and between different bacterial populations is a major health problem on a global scale. The identification of genetic transformation in genomic data from Neisseria meningitidis, the meningococcus (Mc), and other bacteria is problematic, since similar or even identical alleles may be involved. A particular challenge in naturally
transformable bacteria generally is to distinguish between common ancestry and true recombined sites in sampled genome
sequences. Furthermore, the identification of recombination following experimental transformation of homologous alleles
requires identifiable differences between donor and recipient, which in itself influences the propensity for homologous recombination (HR). This study identifies the distribution of HR events following intraspecies and interspecies Mc transformations of rpoB alleles encoding rifampicin resistance by whole-genome DNA sequencing and single nucleotide
variant analysis. The HR events analysed were confined to the genomic region surrounding the single nucleotide genetic
marker used for selection. An exponential length distribution of these recombined events was found, ranging from a few
nucleotides to about 72 kb stretches. The lengths of imported sequences were on average found to be longer following experimental transformation of the recipient with genomic DNA from an intraspecies versus an interspecies donor (P<0.001). The recombination events were generally observed to be mosaic, with donor sequences interspersed with recipient
sequence. Here, we present four models to explain these observations, by fragmentation of the transformed DNA, by
interruptions of the recombination mechanism, by secondary recombination of endogenous self-DNA, or by repair/replication mechanisms.