Phylogenetic Analysis
We first compared the data of the 24 loci MIRU-VNTR against that of MIRU-VNTRplus(https://www.miru-vntrplus.org/MIRU/index.faces). The most frequent pattern found for the Beijing A strain was MLVA type 1048-33, while the less common patterns with SLVs (Table 1) were MLVA types 1048-32 and 342-33 (Table 2). We next searched for these three MLVA types in a compiled 24-MIRU-VNTR global dataset of 4,987 Beijing isolates (Merker et al., 2015) and found that MLVA type 1048-33 was scarce, with only five entries, and remarkably two of were from Panama; 1048-32 was more frequent, 158 isolates widely distributed in Asia and fewer entries from Latin America; 342-3 was poorly represented (12 isolates) (Table 2).
WGS-analysis revealed that Beijing A cluster corresponds to the modern Beijing sublineage, specifically its Asian African 3 (Bmyc13; L2.2.5) sublineage (Figure 2). The entries showing relatedness with Beijing A strains in our study matched Vietnamese isolates (Figure 2). We selected the currently publicly available sequences of MTBC Beijing subgroup L2.2.5/Asian African strains (~ 200 strains) to construct a maximum likelihood phylogeny that grouped, again, Colon Beijing A representatives with strains isolated in Vietnam (Ho Chi Minh City), with a good bootstrap support (96%).
Finally, (Figure 3) we focused on a smaller subset corresponding to the clade that included the Panama Beijing A isolates and related Vietnamese isolates to determine their convergence at a time point between 2000-2012 by BEAST analysis. The resulting median substitution rate was estimated to be 4.0 x 10^-7 [95% HPD 2.75 x 10^-7 - 5.11 x 10-7], which corresponds to 1.6 subs/genome/year (95% confidence interval 1.1 - 2.0/year).