Interplay of the modified nucleotide phosphoadenosine 5′-phosphosulfate (PAPS) with global regulatory proteins in Escherichia coli: modulation of cyclic AMP (cAMP)-dependent gene expression and interaction with the HupA regulatory protein. (25th November 2016)

• Record Type: Journal Article
• Authors: Longo, Francesca; Motta, Sara; Mauri, Pierluigi; Landini, Paolo; Rossi, Elio
• Is Part Of: Chemico-biological interactions. Volume 259:Part A(2016)
• Page Start: 39
• Page End: 47
• Publication Date: 2016-11-25
• Subjects: Phosphoadenosine 5′-phosphosulphate (PAPS) -- Cyclic adenosine monophosphate (cAMP) -- Adenylate cyclase CyaA -- Histone-like HU protein -- Gene expression regulation -- Signal molecule; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2016.04.016
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: In the bacterium Escherichia coli, some intermediates of the sulfate assimilation and cysteine biosynthesis pathway can act as signal molecules and modulate gene expression. In addition to sensing and utilization of sulphur sources, these signaling mechanisms also impact more global cell processes, such as resistance to antimicrobial agents and biofilm formation. In a recent work, we have shown that inactivation of the cysH gene, encoding phosphoadenosine-phosphosulfate (PAPS) reductase, and the consequent increase in intracellular PAPS concentration, strongly affect production of several cell surface-associated structures, enhancing surface adhesion and cell aggregation. In order to identify the molecular mechanism relaying intracellular PAPS concentration to regulation of cell surface-associated structures, we looked for mutations able to suppress the effects of cysH inactivation. We found that mutations in the adenylate cyclase-encoding cyaA gene abolished the effects of PAPS accumulation; consistent with this result, cyclic AMP (cAMP)-dependent gene expression appears to be increased in the cysH mutant. Experiments aimed at the direct identification of proteins interacting with either CysC or CysH, i.e. the PAPS-related proteins APS kinase and PAPS reductase, allowed us to identify several regulators, namely, CspC, CspE, HNS and HupA. Protein-protein interaction between HupA and CysH was confirmed by a bacterial two hybrid system, and inactivation of the hupA gene enhanced the effects of the cysH mutation in terms of production of cell surface-associated factors. Our results indicate that PAPS can modulate different regulatory systems, providing evidence that this molecule acts as a global signal molecule in E. coli . Graphical abstract: Highlights: Phosphoadenosine 5′-phosphosulfate (PAPS) acts as a global signal molecule in Escherichia coli . PAPS accumulation stimulates cAMP-CRP-dependent gene expression. PAPS/cAMP interplay affects composition of bacterial cell surface-associated structures. PAPS (or PAPS reductase) interacts with the global regulator and nucleoid-associated protein HupA.