Regulation of the Histidine Utilization (Hut) System in Bacteria

Abstract

SUMMARY The ability to degrade the amino acid histidine to ammonia, glutamate, and a one-carbon compound (formate or formamide) is a property that is widely distributed among bacteria. The four or five enzymatic steps of the pathway are highly conserved, and the chemistry of the reactions displays several unusual features, including the rearrangement of a portion of the histidase polypeptide chain to yield an unusual imidazole structure at the active site and the use of a tightly bound NAD molecule as an electrophile rather than a redox-active element in urocanase. Given the importance of this amino acid, it is not surprising that the degradation of histidine is tightly regulated. The study of that regulation led to three central paradigms in bacterial regulation: catabolite repression by glucose and other carbon sources, nitrogen regulation and two-component regulators in general, and autoregulation of bacterial regulators. This review focuses on three groups of organisms for which studies are most complete: the enteric bacteria, for which the regulation is best understood; the pseudomonads, for which the chemistry is best characterized; and Bacillus subtilis , for which the regulatory mechanisms are very different from those of the Gram-negative bacteria. The Hut pathway is fundamentally a catabolic pathway that allows cells to use histidine as a source of carbon, energy, and nitrogen, but other roles for the pathway are also considered briefly here.

Acinetobacter baumannii Response to Host-Mediated Zinc Limitation Requires the Transcriptional Regulator Zur

“…One unique group of Zur-regu- lated genes identified in this analysis are those belonging to the Hut system. The Hut system is responsible for the catabolism of histidine to the end products glutamate, ammonia, and formate/ formamide (31). A functional link between histidine catabolism and adaptation to Zn-limiting conditions has yet to be defined.…”

Host Responses to the Pathogen Mycobacterium avium subsp. paratuberculosis and Beneficial Microbes Exhibit Host Sex Specificity

“…Histidine can be catabolized by Firmicutes as a carbon source, producing glutamate and NH 3 ϩ (47, 48). The histidine utilization (Hut) system is highly conserved in bacteria, and those with Hut pathways are able to use histidine as their main source of nitrogen (48). Synthesis of histidine is expensive to a cell, and therefore, catabolism is highly regulated and futile production and excessive catabolism are unwarranted (48).…”

“…Synthesis of histidine is expensive to a cell, and therefore, catabolism is highly regulated and futile production and excessive catabolism are unwarranted (48). As such, high concentrations of histidine are able to inhibit bacterial growth and are especially toxic to organisms that do not have Hut systems, including some enteric food-borne pathogens, such as Escherichia coli and Salmonella, Enterobacter, Shigella, and Proteus species (48). Thus, if exogenous histidine levels are high (like those conditions identified at day 90 in mice fed probiotics) (Fig.…”

“…The histidine utilization (Hut) system is highly conserved in bacteria, and those with Hut pathways are able to use histidine as their main source of nitrogen (48). Synthesis of histidine is expensive to a cell, and therefore, catabolism is highly regulated and futile production and excessive catabolism are unwarranted (48). As such, high concentrations of histidine are able to inhibit bacterial growth and are especially toxic to organisms that do not have Hut systems, including some enteric food-borne pathogens, such as Escherichia coli and Salmonella, Enterobacter, Shigella, and Proteus species (48).…”

Predicting the Biodegradability Nature of Imidazole and Its Derivatives by Modulating Two Histidine Degradation Enzymes (Urocanase and Formiminoglutamase) Activities

“…phenylimidazole and nitro-substitutes imidazoles have been reported to have poor biodegradability nature [5]. The histidine degradation has been reported in several microorganisms including Bacillus subtilis, Enterobacter aerogenes, Pseudomonas aeruginosa, and Pseudomonas fluorescens [14]. Thus, in the present study, imidazole and their derivatives were evaluated on the docking behavior of P. putida urocanase and V. cholera FIGase using PatchDock.…”