cAMP-Dependent Transcription Factor in Mycobacterium tuberculosis Coded by the Rv3676 Gene as a Possible Target for the Development of Antituberculosis Drugs

Abstract

Adenylate cyclase Rv2212 plays a key role in the growth of Mycobacterium tuberculosis (Mtb) and its reactivation from the dormant state. This enzyme could potentially be a good target for the development of new antituberculosis drugs. However, enzymes of this type are also important for the metabolism of the host organism, which makes it doubtful that their inhibitors can be used for treatment of the disease. In the Mtb genome, the cAMP-dependent transcription factor (cAMP-TF), which is encoded by the Rv3676 gene, is annotated and absent in the human organism. The Mtb strain with an overexpression of this gene was designed. This strain rapidly grew in vitro and in vivo under stress conditions. Bacteria of the new strain retained the plasmid with the Rv3676 gene in vivo even in the absence of a selection agent, which indicated the advantages for survival with increased cAMP-TF expression. These results demonstrate the importance of Rv3676 for maintenance of the viability of Mtb cells under unfavorable in vitro conditions and their virulence in vivo and were similar to those obtained by overexpression of the adenylate cyclase Rv2212. Transcription factor Rv3676 may be a new target for the development of new antituberculosis drugs.