Table 1.
Drug resistance-associated genetic regions analyzed.
Figure 1.
Selection of study population.
Grey boxes indicate sample sets used to analyze the strain population structures in the three South African provinces. Boxes with striped pattern indicate sample sets used to characterize drug resistance mutation patterns among XDR-TB associated genotypes. a) Computer-based random sampling was applied. b) Review of an extensive collection of data generated within multiple previous studies.
Figure 2.
Strain population structure of drug-sensitive (DS), mono-/poly-resistant (DR), sensu stricto multidrug-resistant (MDR s.s.; 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.
The R220, R86 and F15/LAM4/KZN genotypes, respectively, represent a subgroup of the typical Beijing, “atypical” Beijing and LAM4 family [14]–[16], [22]–[24]. Based on similar IS6110 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 [23], [25], [27]. 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 [22].
Figure 3.
Drug resistance mutation pattern in a random selection of 193 MDR R86 isolates from the Eastern Cape.
Different colours indicate different drug resistance associated genes. The area of the circles is proportional to the number of isolates (indicated in the centre of each circle) harbouring an identical drug resistance mutation for the respective resistance gene as well as all circles connected to the left. Principal branches of the tree were defined by resistance mutations in pncA. Other first-line drug resistance mutations were connected by logical deduction to maximize clustering and were followed by second-line resistance mutations. However, the order of acquisition of resistance mutations may remain debatable in some cases.
Figure 4.
Drug resistance mutation pattern in a convenience sample of 41 MDR Beijing isolates from the Western Cape.
No data was available for the streptomycin resistance determining region in rrs (Table 1). For more information see figure legend of Figure 3.
Table 2.
Geographical distribution of selected clusters of isolates.
Figure 5.
Model for the evolution of XDR-TB associated strain families.