FIG 1.

The M. tuberculosis whiB6 gene is differentially regulated by PhoP, depending on the genetic background. (A) Schematic representation of ESX-1 and extended ESX-1 genes from M. tuberculosis. The diagram shows genetic regions from whiB6 (rv3862c) to mycP1 (rv3883c), espD (rv3614c) to espA (rv3616c), and espR (rv3849). Genes are represented by filled arrows and colored according to their putative function. Predicted operons are represented by thin arrows. The RD1 region deleted in M. bovis BCG is also indicated. (B) Heat map from microarray comparisons of H37Rv and GC1237 with their respective phoPR mutants. Only genes involved in ESAT-6 production and secretion are reported for clarity. The GC1237 phoPR mutant displays downregulation of most ESX-1 genes. In contrast, the H37Rv reference strain show divergent PhoP regulation of whiB6, esxB (rv3874), esxA (rv3875), eccD1 (rv3877), and espJ (rv3878) (indicated by asterisks) compared to strain GC1237. Note that whiB6 shows the most divergent PhoP regulation between both strains. (C) qRT-PCR analyses showing PhoP regulation over whiB6 in the H37Rv strain compared to those of MT103 and GC1237 clinical isolates. Note the divergent PhoP regulation in clinical strains compared to that of the reference standard H37Rv. Bars indicate fold changes in gene expression relative to the sigA gene used as endogenous control. Results represent the average of three independent experiments, and error bars indicate the standard deviation (SD) of the mean.