Promoter- and attenuator-related metabolic regulation of the Salmonella typhimurium histidine operon

Abstract

Expression of the histidine (his) operon in Salmonella typhimurium was found to be positively correlated with the intracellular level of guanosine tetraphosphate (ppGpp). Limitation for amino acids other than histidine elicited a histidineindependent metabolic regulation of the operon. In bacteria grown at decreased growth rates, his operon expression was metabolically regulated up to a point, after which further decreases in growth rate no longer resulted in further enhancement of operon expression. Studies using strains carrying various regulatory and deletion mutations indicated that metabolic regulation is achieved predominantly by increased RNA chain initiations at the primary (P1) and internal (P2) promoters. Metabolic regulation ordinarily did not involve changes in RNA chain terminations at the attenuator site of the his operon. A model is proposed that involves ppGpp-induced changes in RNA polymerase initiation specificity at particular promoters. A second, special form of metabolic regulation may operate which also is histidine independent, but does involve relief of attenuation. Expression of the histidine (his) operon inSalmonella typhimurium is exerted predominantly at the level of mRNA production (22) and appears to involve two major control sites, the primary promoter (P1) and a transcriptional barrier called the attenuator (Atn) (3,22). Thus, overall operon expression involves both the frequency of RNA chain initiations at P1 and the frequency ofpremature RNA chain terminations at Atn (Fig. 1). Data obtained from in vivo and in vitro experiments indicate that mutation hisO2355 at least in part defines the P1 site and deletion hisO1242 defines the Atn site (13,15,22).The model also hypothesizes the existence of a positive factor (46), acting to relieve the transcriptional terminations otherwise occurring at the attenuator (anti-Atn). Three mutational sites, hisO2965, hisO2966, and hisO3148, seem to affect relief of attenuation (13, 22); thus, the site of positive-factor interaction is represented by the broad bracket labeled "Anti-Atn" in Fig.

Mutation spoT of Escherichia coli increases expression of the histidine operon deleted for the attenuator

“…Neither ppGpp nor pppGpp appeared to influence gnd gene expression. The metabolic regulation of the E. coli his operon was found to be similar to the ppGpp-mediated metabolic regulation of the S. typhimurium his operon.Guanosine 5'-diphosphate 3'-diphosphate (ppGpp) has been proposed as a positive effector of Salmonella typhimurium histidine (his) operon transcription both in vitro (21) and in vivo (21,26). The ppGpp-mediated effect on his operon expression in vivo has been termed "metabolic regulation" (21, 26).…”

“…Guanosine 5'-diphosphate 3'-diphosphate (ppGpp) has been proposed as a positive effector of Salmonella typhimurium histidine (his) operon transcription both in vitro (21) and in vivo (21,26). The ppGpp-mediated effect on his operon expression in vivo has been termed "metabolic regulation" (21,26). It has been suggested that ppGpp increases the mRNA initiation frequency from the his operon primary promoter in vivo by possibly acting as a direct effector of RNA polymerase (26).…”

“…The ppGpp-mediated effect on his operon expression in vivo has been termed "metabolic regulation" (21,26). It has been suggested that ppGpp increases the mRNA initiation frequency from the his operon primary promoter in vivo by possibly acting as a direct effector of RNA polymerase (26).…”

Correlation between the Production of α‐Toxin and Growth Rate in Staphylococcus aureus

“…The first one is metabolic regulation, which occurs in cells in different metabolic states, and in the absence of operon-specific regulation, well known in the trp operon expression of Escherichia coli (10) and the his operon expression of Salmonella typhimurium (16). Guanosine tetraphosphate has been proposed as an effector in his operon metabolic regulation of S. typhimurium (16). The second is the growth rate-related catabolite repression reported by Wanner et al (15).…”

“…Growth rate-related production of enzymes or proteins has been studied by many workers (8,10,15,16), and three types of control have been proposed. The first one is metabolic regulation, which occurs in cells in different metabolic states, and in the absence of operon-specific regulation, well known in the trp operon expression of Escherichia coli (10) and the his operon expression of Salmonella typhimurium (16). Guanosine tetraphosphate has been proposed as an effector in his operon metabolic regulation of S. typhimurium (16).…”