Interplay between transcriptional regulators and VapBC toxin-antitoxin loci during thermal stress response in extremely thermoacidophilic archaea

Abstract

Thermoacidophilic archaea lack sigma factors and the large inventory of heat shock proteins (HSPs) widespread in bacterial genomes, suggesting other strategies for handling thermal stress are involved. Heat shock transcriptomes for the thermoacidophilic archaeon Saccharolobus (f. Sulfolobus) solfataricus 98/2 revealed genes that were highly responsive to thermal stress, including transcriptional regulators YtrA_Ss (Ssol_2420) and FadR_Ss (Ssol_0314), as well as type II toxin-antitoxin (TA) loci VapBC6 (Ssol_2337, Ssol_2338) and VapBC22 (Ssol_0819, Ssol_0818). The role, if any, of type II TA loci during stress response in microorganisms, such as Escherichia coli, is controversial. But, when genes encoding YtrA_Ss , FadR_Ss , VapC22, VapB6, and VapC6 were systematically mutated in Sa. solfataricus 98/2, significant up-regulation of the other genes within this set was observed, implicating an interconnected regulatory network during thermal stress response. VapBC6 and VapBC22 have close homologues in other Sulfolobales, as well as in other archaea (e.g. Pyrococcus furiosus and Archaeoglobus fulgidus), and their corresponding genes were also heat shock responsive. The interplay between VapBC TA loci and heat shock regulators in Sa solfataricus 98/2 not only indicates a cellular mechanism for heat shock response that differs from bacteria but one that could have common features within the thermophilic archaea.

Figure 1.. Model of Saccharolobus solfataricus transcriptional regulator and Toxin-Antitoxin heat shock regulatory network.

Based on mutant transcriptional responses to thermal stress, the proposed direct or indirect activation or repression of the transcriptional regulators YtrA_Ss and FadR_Ss, the Toxins VapC6 and VapC22, and the Antitoxin VapB6 by other members of this same group are depicted.

Figure 2.. Overlays of Saccharolobus solfataricus VapC22 and homologs structural predictions.

Structural predictions using the RoseTTAfold option of the Robetta tool. (Left) Overlay of one representative model for each protein of the Sa. solfataricus VapC22 and homologs shown. (Right) Comparison of VapC22 and Msed VapC8. VapC8 is a rRNA degrader.