Bacterial Sirtuins Overview: An Open Niche to Explore

Abstract

Sirtuins are deacetylase enzymes widely distributed in all domains of life. Although for decades they have been related only to histones deacetylation in eukaryotic organisms, today they are considered global regulators in both prokaryotes and eukaryotes. Despite the important role of sirtuins in humans, the knowledge about bacterial sirtuins is still limited. Several proteomics studies have shown that bacterial sirtuins deacetylate a large number of lysines in vivo, although the effect that this deacetylation causes in most of them remains unknown. To date, only the regulation of a few bacterial sirtuin substrates has been characterized, being their metabolic roles widely distributed: carbon and nitrogen metabolism, DNA transcription, protein translation, or virulence. One of the most current topics on acetylation and deacetylation focuses on studying stoichiometry using quantitative LC-MS/MS. The results suggest that prokaryotic sirtuins deacetylate at low stoichiometry sites, although more studies are needed to know if it is a common characteristic of bacterial sirtuins and its biological significance. Unlike eukaryotic organisms, bacteria usually have one or few sirtuins, which have been reported to have closer phylogenetic similarity with the human Sirt5 than with any other human sirtuin. In this work, in addition to carrying out an in-depth review of the role of bacterial sirtuins in their physiology, a phylogenetic study has been performed that reveals the evolutionary differences between sirtuins of different bacterial species and even between homologous sirtuins.

Short prokaryotic Argonautes provide defence against incoming mobile genetic elements through NAD+ depletion

“…About half of all identified short pAgos are associated or fused into a single-chain protein with Sir2-APAZ proteins 8 . The Sir2 domain-containing proteins are widely distributed in all domains of life and perform protein deacetylation or ADP-ribosylation functions using NAD + as a co-factor 20,21 . Particularly, bacterial Sir2 proteins are involved in many cellular processes including transcription, translation, carbon and nitrogen metabolism, virulence and resistance to stress 21 .…”

“…The Sir2 domain-containing proteins are widely distributed in all domains of life and perform protein deacetylation or ADP-ribosylation functions using NAD + as a co-factor 20,21 . Particularly, bacterial Sir2 proteins are involved in many cellular processes including transcription, translation, carbon and nitrogen metabolism, virulence and resistance to stress 21 . Despite the fact that short pAgos, half of which are associated with Sir2 proteins, make up the majority of all pAgos, their function in the cell and in vitro remains to be established.…”

Pangenomic analysis reveals plant NAD+manipulation as an important virulence activity of bacterial pathogen effectors

“…Using HMMER-based approach, 146 candidate OGs were identified, whilst the HHsearch-based approach picked up 564 candidates, including 136 being identified by both approaches (Table 2, full details in Supplemental Table S2). Among the 136 candidates are known housekeeping nucleosidases, such as the NUDIX enzyme NudC (OG1452), the Sirtuin CobB3 (OG752), the purine nucleosidase RihA (OG2649), and cyclic-AMP phosphodiesterase CpdA (OG3903) (Drabinska et al, 2020; Fuchs et al, 2010; Gallego-Jara et al, 2021; Petersen and Moller, 2001). In addition, both searches identified the TIR T3E HopAM1 (OG6638) (Eastman et al, 2022) and the ART T3E HopU1 (OG9885) (Fu et al, 2007).…”

Research progress in inducing immunogenic cell death of tumor cells

“…The most common chemical agent among the Taxol inducers is paclitaxel, which is currently the first-line regimen used in the clinical treatment of breast cancer. It is capable of stabilizing microtubules, causing mitotic cell death, and blocking the G2-M phase cell cycle (95). In experiments with ovarian cancer cells (70), paclitaxel-induced CRT exposure increased ATP expression, extracellular HMGB1 and ANXA1 expression, and other DAMPs in mouse ovarian cancer cells.…”