Mutation rates (×10⁻⁸/cell division), determined with 8 µg/ml rifampicin, for the M. tuberculosis strains used in this study.

<p>Description of the strains can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029108#pone-0029108-t001" target="_blank">Table 1</a>. Red bars indicate replicates from a second, independent experiment.</p

Direcció estratègica i lideratge, febrer 2013

Recurs d'aprenentatge de la Universitat Oberta de Catalunya.Recurso de aprendizaje de la "Universitat Oberta de Catalunya".Learning material of the "Universitat Oberta de Catalunya"

Description of M. tuberculosis strains used in this study.

<p><i>Strains are identified by the name given by either the RIVM (numerical codes) or the KIT (letter+number). DST: drug susceptibility profile, H: isoniazid, R: rifampicin, S: susceptible, R: resistant. The genotype of the strains indicated in the table is determined by spoligotyping, mutations in parentheses are characteristic genotypic mutations identified by MLPA and confirmed by sequencing (ogt, mutT2, mutT4, Ag85C). Mutations in katG confer resistance to isoniazid; deletions were initially picked up by two different PCR reactions, amplifying either the region that covers the drug resistance mutations at codon 315 or the genotypic mutation at codon 463. The notation in this table indicates that the PCR fragment in question was absent and that therefore the region was deleted in the specific strain</i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029108#pone.0029108-Bergval1" target="_blank">[2]</a>.</p

Spectrum of spontaneous rpoB-mutations obtained by method 2 (single colonies from 10-ml cultures).

<p> <i>Results for MTB72 (first row) and strains H103, 2001–2184 and 2001–2185 were obtained in the first experiment, where we assessed the influence of pre-existing INH resistance on the spectrum of mutations. </i><i>Results for MTB72 (second row) and 9900098, 2001-1669 and 2001-1670 were obtained in the second experiment, where we determined the role of the LAM genotype on the spectrum of rpoB-mutations. </i><i>Results for MTB72 (third row) and 9500592, 2002-1640, 2002-1585 and 17583 were obtained in the third experiment, where we determined the role of the Beijing genotype on the spectrum of rpoB-mutations. ins: insertion, indel: combined insertion/deletion, Δ: deletion.</i></p

Proportion of rpoB-S531L and other mutations in rpoB acquired by INH-resistant M. tuberculosis strains compared to their susceptible parent strains.

<p>Results for all INH-resistant strains are grouped, as well as the results for are wildtype strains. Mutation distribution obtained for the INH-resistant group and the wildtype group and rpoB mutation distribution obtained for the two different experimental methods are compared. The red bars depict the proportion of rpoB-S531L mutations that were detected. The blue bars represent all other rpoB-mutations, whereas for the X² test depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029108#pone-0029108-t004" target="_blank">tables 4</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029108#pone-0029108-t005" target="_blank">5</a> only the four most prevalent mutations were taken into account. Numbers in the bar graphs represent the number of samples carrying the specific mutation as a percentage of the total amount of rpoB mutants and as absolute numbers (in brackets). The p-values above the bar graphs represent the probability that the distributions compared are similar.</p

Probability of an equal distribution of the four targeted rpoB mutations in various M. tuberculosis strains.

<p> <i>The probability (p_a) of hypothesis h0_a (the targeted rpoB-mutations (S531L, H526D, H526Y and S522L) have an equal chance of occurring) was determined by X² for each strain for both method 1 and method 2. For all tested strains, except in the first experiment with MTB72, the statistical power of the X² test was reduced due to one or more mutations occurring less than five times. NA: not available, mutants were not obtained for these strains. </i><b><i>Bold</i></b><i>: p_a<0.05, therefore hypothesis is rejected.</i></p

Probability of the spectrum of rpoB mutations in the INH-resistant mutant and the wildtype parent being identical.

<p> <i>The probability of hypothesis h0_b (the spectrum of rpoB-mutations of the INH-resistant mutant is not different than that of the wildtype parent) determined by X² for all INH-resistant strains for both methods. For all of the tested strains the statistical power of the X² test was reduced due to one or more mutations occurring less than five times. NA: not available, mutants were not obtained for these strains.</i></p><p>*<i>: since both 2001-1669 and 2001-1670 are resistant to INH (via katG-S315T), the spectrum was compared to the only susceptible LAM strain, 9900098. </i><b><i>Bold</i></b><i>: p_a<0.05, therefore hypothesis is rejected.</i></p

Correspondence table between the different <i>M</i>. <i>tuberculosis</i> taxonomies.

<p>The items in italics were subsequently added according to findings in complementary analyses. Parts under brackets indicate synonyms. Complete sublineages under brackets indicate imprecise correspondance. “?” indicate hypotheses with no actual proof.</p><p>Correspondence table between the different <i>M</i>. <i>tuberculosis</i> taxonomies.</p

TBminer Lineage Prediction tool: the output file.

<p>TBminer Lineage Prediction tool: the output file.</p

Major clusters of the 2004–2008 Netherlands RIVM collection (n≥10).

<p>24-VNTR clusters ID numbers were attributed according to their size (n°1 for the largest). Isolates ID are those stated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130912#pone.0130912.s002" target="_blank">S1 Table</a>. SIT = Short International Type.</p><p>Major clusters of the 2004–2008 Netherlands RIVM collection (n≥10).</p