Absolute numbers and proportions of pulmonary and extrapulmonary TB.

<p>The number of unknown location is presented for completeness and was subtracted from the total number of patients before calculating the proportions.</p>a<p>includes some patients with both pulmonary and extrapulmonary TB.</p

Proportion of extrapulmonary site of TB of the eight studies which reported on both, cases caused by <i>M. bovis</i> and <i>M. tuberculosis</i> (gray lines combine data from the same studies).

<p>The circle diameter is proportional to the number of patients included in the study.</p

World map with the origin of data included in this study.

<p>World map with the origin of data included in this study.</p

Proportion of extrapulmonary sites of TB per WHO region (n = the number of studies per region).

<p>The circle diameter is proportional to the number of patients included in the study. The diamond represents the median proportion of the respective region. *significant differences exists only between the WHO regions America and Western Pacific (two sample Wilcoxon signed rank test, n = 10, W = 21, p = 0.017).</p

Phylogenetic reconstruction of the evolutionary relationships between the members of the pe and ppe protein families.

<p>A. Phylogeny of the ppe protein family. The phylogenetic tree was constructed from the phylogenetic analysis done on the 180 aa N-terminal domains of the ppe proteins. The tree was rooted to the outgroup Rv3873 (ppe68), shown to be the first ppe insertion into the ESAT-6 (esx) gene clusters <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030593#pone.0030593-GeyvanPittius1" target="_blank">[8]</a>. Figure reproduced from reference 8 with permission of the authors. B. Phylogeny of the pe protein family. The phylogenetic tree was constructed from the phylogenetic analysis done on the 110 aa N-terminal domains of the pe proteins. The tree was rooted to the outgroup Rv3872 (pe35), shown to be the first pe insertion into the ESAT-6 (esx) gene clusters <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030593#pone.0030593-GeyvanPittius1" target="_blank">[8]</a>. Figure reproduced from reference 8 with permission of the authors.</p

Details of 18 whole genome sequence isolates used for <i>in silico</i> comparative gene analysis.

<p>Each analysed genome sequence is listed along with its lineage number <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030593#pone.0030593-Comas2" target="_blank">[78]</a>, Principal Genetic Group (PGG) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030593#pone.0030593-Sreevatsan1" target="_blank">[2]</a> and family group.</p

Details of the <i>pe</i> and <i>ppe</i> genes examined by whole gene sequencing.

*<p> <b>As defined in reference </b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030593#pone.0030593-GeyvanPittius1" target="_blank">[<b>8</b>]</a><b>.</b></p><p>Each gene sequenced in this study is listed along with its phylogenetic position within its family and any additional information regarding its protein's function available in the literature.</p

Details of clinical isolates used in this study.

<p>Each clinical isolate along with its lineage number <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030593#pone.0030593-Comas2" target="_blank">[78]</a>, PGG group <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030593#pone.0030593-Sreevatsan1" target="_blank">[2]</a>, spoligotype family group status <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030593#pone.0030593-Brudey1" target="_blank">[88]</a> and South African IS<i>6110</i> lineage <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030593#pone.0030593-Streicher1" target="_blank">[84]</a> is listed.</p

Drug resistance mutation pattern in a convenience sample of 41 MDR Beijing isolates from the Western Cape.

<p>No data was available for the streptomycin resistance determining region in <i>rrs</i> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone-0070919-t001" target="_blank">Table 1</a>). For more information see figure legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone-0070919-g003" target="_blank">Figure 3</a>.</p

Strain population structure of drug-sensitive (DS), mono-/poly-resistant (DR), <i>sensu stricto</i> multidrug-resistant (MDR <i>s.s.</i>; excluding identified pre-XDR and XDR isolates), pre-extensively drug-resistant (pre-XDR) and extensively drug resistant (XDR) isolates in three provinces of South Africa.

<p>The R220, R86 and F15/LAM4/KZN genotypes, respectively, represent a subgroup of the typical Beijing, “atypical” Beijing and LAM4 family <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone.0070919-Strauss1" target="_blank">[14]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone.0070919-Pillay1" target="_blank">[16]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone.0070919-Muller2" target="_blank">[22]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone.0070919-Gandhi2" target="_blank">[24]</a>. Based on similar IS<i>6110</i> RFLP patterns and whole genome sequencing data it was previously shown that “atypical” Beijing strains in the Western and Eastern Cape, unlike in other parts of the world, represent one single genotype herein referred to as R86 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone.0070919-Chihota1" target="_blank">[23]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone.0070919-Ioerger1" target="_blank">[25]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone.0070919-Klopper1" target="_blank">[27]</a>. The specific presence of R220 and F15/LAM4/KZN genotypes was only assessed in the Western Cape and KwaZulu-Natal, respectively, where these genotypes were known to be frequent among XDR-TB cases <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070919#pone.0070919-Muller2" target="_blank">[22]</a>.</p