Regulatory circuits involved with pH-regulated gene expression in Salmonella typhimurium

Abstract

Salmonella typhimurium encounters a variety of acid conditions during both its natural and pathogenic existence. The ability of this organism t o respond transcriptionally to low pH is an area of active interest but little knowledge. As part of an ongoing investigation of low-pH adaptation, 18 pH-controlled IacZ operon fusions in Salmonella typhimurium have been identified (15 in this study) and categorized into a t least 11 different loci. They include iroA (at 57 min), aciA (99 min), aciB (90-93 min), aciD (ompC, 45 min), acil, aciK (33-36 rnin), aniC (93 min), anil(33-36 min), hyd (59 min), cadA (54 min) and aniG (63 rnin). All but two were induced by low pH. One of the exceptions, the iron-regulated iroA locus, was induced a t high pH. The unusual aciA locus was induced by low pH under semiaerobic conditions but high pH under aerobic conditions. Most of the other aci genes were expressed best under anaerobic conditions. Many of these genes exhibited strict co-inducer requirements for small molecules to be expressed in minimal medium. These included iron for iroA, tyrosine for aniC, I and aciK, mannose for aniG, formate for hyd, lysine for cadA, and unknown components of complex medium for aciA, aciB and aciD. Six regulatory circuits were revealed involving a t least five regulatory loci (fur, oxrG, earAB, earC and ompR). As part of the adaptive response to low pH, 5. typhimurium will induce an acid protection system called the acid tolerance response (ATR). As has been shown for fur mutations, the oxrG regulatory mutation interfered with the normal induction of this system.

The role of fur in the acid tolerance response of Salmonella typhimurium is physiologically and genetically separable from its role in iron acquisition

“…Further evidence for this is found in Table 2, which illustrates the effects of loss-offunction fur (fur-2), superrepressor fur (fur s -15), and iron-blind fur-9 mutations on the expression of a hyd-lacZ fusion. We have previously shown that the hyd locus is coinduced by acid and anaerobiosis and that Fur is required for hyd induction at pH 5.8 (19). This finding is confirmed in Table 2 (JF2392).…”

“…This conclusion is based on the ability of the H90R Fur mutant to mediate acid induction of specific Fur-dependent ASPs and enable induction of acid tolerance in spite of the fact that the mutant Fur cannot mediate iron regulation. We have also provided evidence that Fur can, either directly or indirectly, act as a positive regulator of the pH-regulated locus, hyd (19). This acid control also appears to be iron independent in that a Fur superrepressor and the iron-blind Fur H90R still regulated hyd in response to pH.…”

“…When intracellular Fe(II) concentrations are high, iron-metallated Fur complex binds to a 19-bp DNA consensus sequence, the Fur box, in the promoter region of the iron acquisition genes to repress their transcription (1,5,9,21,43). However, reports from several laboratories, including our own, suggest that the role of Fur in cellular physiology extends beyond that of regulating iron utilization (18,19,23,32,37,47,49,51,53). The focus of this study was to further define the roles of Fur and iron in regulating the ATR.…”

Arginine-Agmatine Antiporter in Extreme Acid Resistance in Escherichia coli

“…Here we identify the gene coding for the E. coli arginine-agmatine exchanger used in XAR, a membrane protein spanning 12 amino acids of unknown function, designated yjdE (b4115) and now named adiC by us and, recently, by others (12). The adiC gene is a homologue of a gene, aniC, in Salmonella enterica serovar Typhimurium that is conjectured to be the possible arginine-agmatine exchanger in arginine XAR (25) and was previously identified from a genetic analysis by using lacZ transcriptional fusion proteins activated under conditions of low pH (10). We show that adiC functions specifically in arginine XAR and that the dependence of transport activity on arginine concentration and pH naturally accounts for its role in maintaining cell viability under strong acid stress conditions.…”

Factors affecting haemolysin production and Congo red binding in Salmonella enterica serovar Typhimurium DT 98

“…At least six regulatory classes of nutrient, starvation-inducible loci have been characterised for the salmonellae [7]. To assign biological significance to any putative character or virulence determinant, it is necessary to demonstrate its expression and sometimes its extracellular release in relation to host environmental cues or in appropriate ecological settings.…”