Figure 4.

A selection of existing configurations of the ppe38‐71 locus. Gene numbers correspond to the M. tuberculosis CDC1551 reference genome. ppe38 (orange) and ppe71 (yellow) are genetically identical except for a 21bp deletion (blue) in ppe71. The two esx‐genes (green) have been named esxX and esxY based on standardized nomenclature (Bitter et al., 2009; Ates et al., 2018b). The most common configuration of the locus is depicted at the top (McEvoy et al., 2009a). The H37Rv reference genome (second line) is misannotated as having only one copy of ppe38, but multiple H37Rv strains were shown to possess the CDC1551‐like locus (Box 1; McEvoy et al., 2009a; Ates et al., 2018b). However, the configuration of a single copy of either ppe38, or ppe71, does occur due to recombination in diverse clinical isolates and is referred to as RvD7 (McEvoy et al., 2009a). An RD5‐like deletion that truncates ppe38, but keeps ppe71 intact, was found in certain L4 isolates. This polymorphism did not negatively affect PPE38‐dependent secretion (Lee et al., 2015; Ates et al., 2018c). Similarly, in an ancestral L2‐isolate (SAWC_2088) an IS6110 (black) insertion truncation ppe38 does not negatively affect PPE‐38‐dependent secretion. Subsequent recombination that occurred at the branching point of the modern L2‐lineages, have also truncated ppe71 and deleted esxXY, resulting in a loss of PPE38‐dependent secretion (McEvoy et al., 2009a; Ates et al., 2018b). It should be emphasized that many more configurations of the ppe38‐71 locus, including different RD5‐like deletions have been more thoroughly described in McEvoy et al., 2009b (McEvoy et al., 2009a).