Involvement of Fnr and ArcA in anaerobic expression of the tdc operon of Escherichia coli

Abstract

Anaerobic expression of the tdcABC operon in Escherichia coli, as measured by LacZ activity from single-copy tdc-lacZ transcriptional and translational fusions, is greatly reduced in strains lacking two global transcriptional regulators, Fnr and ArcA. The nucleotide sequence of the tdc promoter around ؊145 shows significant similarity with the consensus Fnr-binding site; however, extensive base substitutions within this region had no effect on Fnr regulation of the tdc genes. A genetic analysis revealed that the effect of Fnr on tdc is not mediated via ArcA. Furthermore, addition of cyclic AMP to the anaerobic incubation medium completely restored tdc expression in fnr and arcA mutants as well as in strains harboring mutations in the Fnr-and ArcA-dependent pfl gene and the Fnr-regulated glpA and frd genes. These results, taken together with the earlier finding that tdc expression is subject to catabolite repression by intermediary metabolites, strongly suggest that the negative regulatory effects of mutations in the fnr and arcA genes are mediated physiologically due to accumulation of a metabolite(s) which prevents tdc transcription in vivo.When incubated anaerobically, Escherichia coli, a typical facultative anaerobe, represses a wide array of aerobic genes and concomitantly expresses certain others which encode key enzymes and proteins needed for anaerobic metabolism. Two global transcriptional regulators, Fnr (fumarate and nitrate reductase activator) and ArcA (a member of the two-component ArcBA sensor-regulator system), have generally been implicated in activating a large number of anaerobic genes and repressing many aerobic genes in oxygen-limiting growth conditions, respectively (reviewed in references 9, 15, 36, and 40). These regulatory proteins appear to have their individual specificities in regulating groups of genes and/or regulons. However, several operons in E. coli are under complex dual control of Fnr and ArcA. Both proteins serve as transcriptional activators of the pfl operon (30), whereas Fnr represses the cydAB operon while ArcA activates its transcription (9). A recent study on the expression of several aerobic and anaerobic respiratory pathway genes as a function of oxygen concentration revealed that Fnr functions optimally at low oxygen saturation, whereas ArcA controls gene expression at higher levels of oxygen (39). It is interesting that the anaerobic activation of arcA transcription is increased three-to fourfold in the presence of Fnr (2). These data clearly suggest that these two regulatory proteins are involved in overall coordination of expression of various anaerobic and aerobic genes in response to the varying oxygen status of the cell.

Comparison of the Changes in Global Gene Expression of <i>Escherichia coli</i> Induced by Four Bactericidal Agents

“…These genes are also induced under conditions of anaerobic growth in rich media [Chattopadhyay et al, 1997].…”

The Complexities of Porin Genetic Regulation

“…Chattopadhyay et al, 1997]. Fnr positively regulates the expression of ompD under anaerobiosis by a post-transcriptional regulatory mechanism that probably acts through mRNA stability [Santiviago et al, 2003].…”

FNR Is a Global Regulator of Virulence and Anaerobic Metabolism inSalmonella entericaSerovar Typhimurium (ATCC 14028s)

“…However, upon sudden reappearance of oxygen, these cellular processes must be reversed in a precise and orderly fashion to ensure the safe transition to the oxygenated environment. This complex regulatory system has been extensively studied in E. coli, where the DNA-binding protein FNR (6,27,44), encoded by fnr, senses changes in [O 2 ] and controls the expression of the different genes either alone or in cooperation with other regulators, e.g., ArcA (11,15,30,32,42,74). Recently, three independent studies have examined the global changes in gene expression in E. coli strain MC4100 (70) and strain MG1655 (14,43) in response to mutations in fnr.…”