Phylogeographic variation in recombination rates within a global clone of methicillin-resistant Staphylococcus aureus

Abstract

Background: Next-generation sequencing (NGS) is a powerful tool for understanding both patterns of descent over time and space (phylogeography) and the molecular processes underpinning genome divergence in pathogenic bacteria. Here, we describe a synthesis between these perspectives by employing a recently developed Bayesian approach, BRATNextGen, for detecting recombination on an expanded NGS dataset of the globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clone ST239.

Results: The data confirm strong geographical clustering at continental, national and city scales and demonstrate that the rate of recombination varies significantly between phylogeographic sub-groups representing independent introductions from Europe. These differences are most striking when mobile non-core genes are included, but remain apparent even when only considering the stable core genome. The monophyletic ST239 sub-group corresponding to isolates from South America shows heightened recombination, the sub-group predominantly from Asia shows an intermediate level, and a very low level of recombination is noted in a third sub-group representing a large collection from Turkey.

Conclusions: We show that the rapid global dissemination of a single pathogenic bacterial clone results in local variation in measured recombination rates. Possible explanatory variables include the size and time since emergence of each defined sub-population (as determined by the sampling frame), variation in transmission dynamics due to host movement, and changes in the bacterial genome affecting the propensity for recombination.

Figure 1

Results of the recombination analysis for the 165 ST239 isolates. The names of the strains are shown on the left and are colored according to the geographic source as follows: red, Asia; yellow, Eastern Europe; green, Western Europe; cyan (light blue), South America; dark blue, Turkey. The colored bars in the panel on the right side of the dendrogram denote the recombination events in the strains along the genome. The coloring of the bars at a specific genomic location reflects the clustering of the recombination events into groups, and is unrelated to either the coloring of the strain names or other bars at distant genomic locations. The asterisks indicate well-known MGEs: the SCCmec element, the phage φSa1 (TW20) and the phages φSaβ-TW20/φSpβ-like.

Figure 2

Functions affected by recombination. The bars are the most inclusive categories based on an adapted version of Riley's classification. The blue section of the bars represents the percentage of genes of each functional category affected by recombination. The 'extrachromosomal' category was here renamed 'MGE' to avoid confusion as these genes are physically located on the chromosome.

Figure 3

The maximum likelihood phylogeny of the ST239 isolates. The tree is based on the SNPs that were not affected by recombination using either BRATNextGen or the method used in [1]. The color coding of the branches is as follows: red, Asia; yellow, Eastern Europe; green, Western Europe; cyan (light blue), South America; dark blue, Turkey; brown, USA; the black branches refer to Australia (ANS46), Egypt (H24), and Syria (M592). The particular country of origin for each isolate is given in Additional file 1. The grey rectangle shows all the strains within Bayesian Analysis of Population Structure (BAPS) group number one (Turkish clade), the pink rectangle covers the strains composing BAPS group number 3 (Asian clade), and the light green rectangle shows the strains found in BAPS group number 2 (South American clade). For the sake of clarity the bootstrap values (bv) are only shown for the three main clades and some minor groups. The scale bar represents substitutions per SNP.

Figure 4

The maximum likelihood tree of the newly sequenced Turkish isolates. Branch color coding is as follows: green, Izmir; dark blue, Ankara; light blue, Istanbul European side; brown, Istanbul Asian side. Only the 71 newly sequenced isolates from Turkey were considered and so the Turkish isolates used in the study by Harris et al. [2] and the western European isolates were excluded for this analysis. The scale bar represents substitutions per SNP. Only for the Izmir group the bootstrap value (bv) is given for simplicity's sake.

Figure 5

The r/m ratios for the BAPS groups and for the analysis of two founder events. (a,b) The r/m figure for each BAPS group with (a) and without MGE (b). (c,d) The r/m values for the two founder events within the Turkish group with (c) and without MGE (d). The arrows specify the comparisons between the different sets. Red arrows show comparisons that are significant at <0.0001, brown arrows those significant at <0.05 and green arrows those that are not significant (P-value >0.05). Of note, the scale of the y-axis is different for each panel.