Overexpression of DosR in Mycobacterium tuberculosis does not affect aerobic replication in vitro or in murine macrophages

Mycobacterium tuberculosis H37Rv, constitutively expressing a second copy of the transcriptional regulator DosR (Rv3133c) under control of the hsp60 promoter, was compared to wild-type M. tuberculosis for in vitro expression of the target genes of the DosR dormancy regulon, for its in vitro growth characteristics in liquid 7H9 culture medium, and for its capacity to replicate in murine macrophages. Under aerobic conditions, hsp60-driven DosR significantly induced the expression of 39 out of 44 DosR regulon genes, as assessed by real time qPCR. Increased DosR regulon gene transcription in vitro did not modify the capacity of the strain to grow under axenic conditions nor to infect murine macrophages as compared to unmodified wild-type bacteria.