Transcription of the _TAC_ operon is induced by several relevant stress conditions including DNA damage [69], heat shock [70], nutrient starvation [43], hypoxia [16], drug-persistence [12], and in host phagocytes [71]. The _TAC_ operon is under the control of two known promoters: the _higB1P_1 located 51 nucleotides upstream of the start codon of _higB1_, thus, controlling the expression of _higB1-higA1-Rv1957_, and the more distal promoter _higB1P_2 located 29 nucleotides upstream of the start codon of the upstream _Rv1954a_[69]. Noticeably, the DNA-damage inducible P1 promoter possesses a RecA-NDp motif characteristic of LexA/RecA-independent genes in _M. tuberculosis_[69]. As observed for most TA loci, _TAC_ is autorepressed by HigA1 binding to a palindromic motif overlapping the -35 element of the _higB1P_2 promoter [65]. Although very likely, it is not known whether HigB1 and/or Rv1957 also participate in this process (Figure 2). A role for HigA1 as a global transcriptional regulator has been proposed as well. Indeed, microarray analysis of the _TAC_ mutant revealed that the _fadB_, _Rv3173c_ and _Rv3662c_ genes might be regulated by HigA1 [65]. Moreover, a one-hybrid reporter system showed that HigA1 is capable of interacting specifically with the promoter region of gene clusters containing stress response genes _whiB7_, _rubA_, _rubB_, and fatty acid metabolism genes _echA20_, _fadE28_, _fadE29_, _ufaA2_, and _fad26_[72]. Finally, ChIP-Seq analysis using FLAG-tagged HigA1 expressed in _M. tuberculosis_ H37 Rv revealed at least 30 potential HigA1 binding sites in intergenic regions, including the _higBA3_ locus described above (TB Database sever). These data suggest that HigA could be part of a network of stress-associated regulons involved in _M. tuberculosis_ pathogenesis. As stated above, Rv1957 shares sequence similarities with the export chaperone SecB known to facilitate protein export in most Gram-negative bacteria. In _E. coli_, the homotetrameric SecB chaperone binds unfolded presecretory proteins, maintains them in a protected yet nonnative state and passes them to the SecA subunit of the Sec translocase, thus facilitating their export [73, 74, 75]. Remarkably, it has been shown that Rv1957 can functionally replace SecB during protein export _in vivo_ in _E. coli_ and prevent aggregation of the outer membrane protein precursor proOmpC _in vitro_[64]. Similarly, the SecB-like protein SmegB from _M. smegmatis_ was also capable of performing such SecB-like function in _E. coli_[66]. The presence of a well-defined outer membrane and a remarkably large number of putative outer membrane proteins in _M. tuberculosis_ and _M. smegmatis_[76, 77, 78] suggests that these bacteria could make use of a functional export chaperone under certain circumstances (Figure 2). Although nothing is known yet about such a role in protein export, an attractive possibility is that SecB-like chaperones specifically connect the activation of stress-responsive TA systems to the export process. Under certain stress affecting the Sec translocon, the cytoplasmic accumulation of certain presecretory proteins could thus compete with HigA1 for binding to the Rv1957 chaperone, facilitating degradation of the free antitoxin and the subsequent activation of the toxin (Figure 2). The relatively well-conserved association of SecB-like chaperones with stress-responsive TA systems, including members of the HigBA, HicAB, and MqsRA families [66] further suggests that the control of TA activation by molecular chaperones might represent a more commonly used mechanism to control bacterial growth in response to environmental changes affecting protein homeostasis. In agreement with such a hypothesis, it was recently shown that the major _E. coli_ stress chaperone DnaK (HSP70) interacts with at least four antitoxins _in vivo_, namely MazE, RelB, MqsA and DinJ, whose respective toxin partners MazF, RelE MqsR, and YafQ were shown to affect translation [79].