The role of bacterial antizyme: From an inhibitory protein to AtoC transcriptional regulator

Abstract

This review considers the role of bacterial antizyme in the regulation of polyamine biosynthesis and gives new perspectives on the involvement of antizyme in other significant cellular mechanisms. Antizyme is a protein molecule induced by the end product of the enzymic reaction that it inhibits, in a non-competitive manner. The bacterial ornithine decarboxylase is regulated by nucleotides, phosphorylation and antizyme. The inhibition of ornithine decarboxylase by antizyme can be relieved to different degrees by DNA or by a variety of synthetic nucleic acid polymers, attributed to a specific interaction between nucleic acid and antizyme. Recently, this interplay between bacterial antizyme and nucleic acid was determined by discerning an additional function to antizyme that proved to be the atoC gene product, encoding the response regulator of the bacterial twocomponent system AtoS-AtoC. The gene located just upstream of atoC encodes the sensor kinase, named AtoS, that modulates AtoC activity. AtoC regulates expression of atoDAEB operon which is involved in short-chain fatty acid metabolism. Antizyme is thus referred to as AtoC, functioning both as a post-translational and transcriptional regulator. Also, the AtoS-AtoC signal transduction system in E. coli has a positive regulatory role on poly-(R)-3-hydroxybutyrate biosynthesis. The properties and gene structural similarities of antizymes from different organisms were compared. It was revealed that conserved domains are present mostly in the C-domain of all antizymes. BLAST analysis of the E. coli antizyme protein (AtoC) showed similarities around 69-58% among proteobacteria, g-proteobacteria, enterobacteria and the thermophilic bacterium Thermus thermophilus. A working hypothesis is proposed for the metabolic role of antizyme (AtoC) describing the significant biological implications of this protein molecule. Whether antizymes exist to other enzymes in different tissues, meeting the criteria discussed in the text remains to be elucidated. ReviewIn 1978 Seymour Cohen, the father of the field of polyamines posed the question "what do the polyamines do?" in his excellent article [1]. Since then, thousands of papers appeared in the literature concerning the metabolic role of polyamines. We will not attempt to discuss all the recent progress in the field, which has been well documented in book form [2][3][4][5][6][7][8] as well as in a number of excellent reviews [9][10][11][12][13][14][15]. Instead, we shall only consider the role of antizyme (Az) in the regulation of ornithine decarboxylase (L-ornithine carboxylyase, EC 4.1.1.17, ODC), its involvement in the bacterial two-component signal transduction system AtoS-AtoC [16], as well as its implication in other significant cellular functions.

Low mutational load and high mutation rate variation in gut commensal bacteria

“…Of these targets, mutations in the last two have previously been observed during adaptation of E. coli to the gut of immune-competent or immunocompromised mice [40,41]. Many of the adaptive targets are functionally important for regulating carbon (dgoR, frlR, atoC, and, potentially, the cad operon) [77,[83][84][85] or nitrogen metabolism (ptsP and tdcA/tdcR) [79,86,87], stress resistance (ptsP, cad operon, ycbC, and, potentially, atoC), and peptidoglycan biogenesis (ycbC) [77,[83][84][85]. Interestingly, ptsP, atoC, and the cad operon appear to be involved in regulating both nutritional competence and stress resistance, which suggests that such mutations may modulate a potential trade-off between nutritional competence and stress resistance, which is well described in in vitro experiments and which is also thought to be important in vivo [81,82,88].…”

Regulation of the Escherichia coli AtoSC two component system by synthetic biologically active 5;7;8-trimethyl-1;4-benzoxazine analogues

“…The protein levels of AtoC in the cell extracts were monitored by immunoblotting using affinitypurified rabbit polyclonal anti-AtoC antibody. 2 As shown in Figure 7a, atoC transcriptional activation also produced increased AtoC accumulation. This indicates that compound 4a under these specific culture conditions does not enhance AtoC degradation.…”

“…31 Proteins were transferred to immobilon PVDF membranes 32 and immunostained with the rabbit polyclonal antibodies against, DnaK, Hsp60, AtoC and AtoS, respectively, prepared as described. 2,11,33 Supplementary data Supplementary data ( 1 H and 13 C NMR spectra for compounds 2a, b, 3a, b, 4a-c, 5a, b, 6a, b, and 7-13) associated with this article can be found, in the online version, at doi:10.1016/j.bmc.2011. 06.029.…”

“…1 His-398 is lying in proximity to the AtoC Asp-55 residue upon AtoSC interaction for the subsequent phosphotransfer and AtoC phosphorylation necessary for AtoSC regulatory actions, 2 the transcriptional regulation of the atoDAEB operon that encode for proteins involved in short-chain fatty acid metabolism. [2][3][4][5] By governing the atoDAEB operon;this system regulates;amongst others;the biosynthesis and the intracellular distribution of cPHB, 6,7 the flagella synthesis; 8 the chemotactic behaviour and the involvement of extracellular Ca 2+ on cPHB synthesis regulated by the AtoSC system. 9 We have recently reported the regulation of the AtoSC system by polyamines and histamine, as cellular components that enable pathogenic bacteria to survive and overcome host defence mechanisms.…”

Low Mutational Load Allows for High Mutation Rate Variation in Gut Commensal Bacteria

“…Of these targets, mutations in the last two have previously been observed during adaptation of E. coli to the gut of immune-competent or immunocompromised mice [34,36]. Many of the adaptive targets are functionally important for regulating carbon ( dgoR, frlR, atoC and, potentially, the cad operon) [67,[74][75][76] or nitrogen metabolism ( ptsP and tdcA/tdcR ) [69,77,78], stress resistance ( ptsP, cad operon, ycbC and, potentially, atoC ) and peptidoglycan biogenesis ( ycbC ) [67,[74][75][76]. Interestingly, ptsP, atoC and the cad operon appear to be involved in regulating both nutritional competence and stress resistance, which suggests that such mutations may modulate a potential trade-off between nutritional competence and stress resistance, which is well described in in vitro experiments and which is also thought to be important in vivo [71,72,79].…”