Disease relevance of algR

• Mucoid Pseudomonas aeruginosa in cystic fibrosis: mutations in the muc loci affect transcription of the algR and algD genes in response to environmental stimuli [1].
• The algR gene, which regulates mucoidy in Pseudomonas aeruginosa, belongs to a class of environmentally responsive genes [2].
• The algR gene was subcloned and sequenced by creating a set of nested deletions in M13 bacteriophage [2].
• The algR gene was overexpressed in Escherichia coli, its product (AlgR) was purified by utilizing its apparent affinity for heparin, and its sequence was verified by partial amino acid sequence analysis [3].

High impact information on algR

• Two positive activators for alginate synthesis, algB and algR, are members of a superfamily of response regulators of the two-component regulatory system [4].
• Few fragment length classes were seen for the alg60-, algR- and toxA-encoding SpeI fragments [5].
• The algR gene product, which controls transcription of a key alginate biosynthetic gene, algD, is homologous to the activator members of the two-component, environmentally responsive systems (NtrC, OmpR, PhoB, ArcA, etc) [1].
• These results suggest that the lasB gene and the alginate system are co-ordinately regulated at a level parallel to or above the algR gene [6].
• In this report, we show that mutations in the muc loci, (muc-2, muc-22, and muc-23, in the standard genetic P. aeruginosa strain PAO, as well as a mapped muc allele in an isolate from a cystic fibrosis patient) affect transcription of algD and algR [1].

Biological context of algR

• Two-dimensional gel analysis of P. aeruginosa algR mutant and wild-type protein extracts revealed 47 differentially regulated proteins, suggesting that AlgR plays both a positive role and a negative role in gene expression [7].
• Mutations in algR result in a nonmucoid phenotype and loss of twitching motility [7].
• Therefore, to determine the effect of algR on P. aeruginosa virulence, an algR mutant was examined for sensitivity to reactive oxygen intermediates, killing by phagocytes, systemic virulence, and the ability to maintain a murine lung infection [7].
• We have cloned and characterized the A. vinelandii algR gene; the deduced amino acid sequence of the protein encoded by this gene shows 79% identity with its P. aeruginosa homolog [8].
• In both mucoid and nonmucoid P. aeruginosa strains (containing a functional algR gene), transcriptional activation of algD increased as the osmolarity of the culture medium increased [9].

Anatomical context of algR

• Mutations in algB, algR, and algT resulted in nonmucoid derivatives, yet algT mutants expressed flagella [10].

Associations of algR with chemical compounds

• Additionally, the algR mutant (PAO700) was more sensitive to hypochlorite [7].
• An insertion downstream of algR produced a strain showing reduced induction of mucoidy in response to growth on nitrate as the nitrogen source [11].
• Additionally, direct measurement of hydrogen cyanide (HCN) production showed that P. aeruginosa PAO1 produced threefold-less HCN than did its algR deletion strain [12].
• The predicted phosphorylation site of AlgR (aspartate 54) and a second aspartate (aspartate 85) in the receiver domain of AlgR were mutated to asparagine, and mutant algR alleles were introduced into the chromosome of P. aeruginosa strains PAK and PAO1 [13].

Regulatory relationships of algR

• Using the algD-xy1E transcriptional fusion the algD promoter was demonstrated to be under positive control by the algR gene [14].

Other interactions of algR

• The algQ gene was found closely linked to the previously identified algR gene [15].
• Insertional inactivation of rpoN (ntrA) in PAO568 did not affect algR and algD transcription [16].
• The proximal promoter of algR was also shown to depend on algU [17].
• Further analysis showed that the stable twitching-defective variants of lasI and rhlI mutants had arisen as a consequence of secondary mutations in vfr and algR, respectively, both of which encode key regulators affecting a variety of phenotypes, including twitching motility [18].

Analytical, diagnostic and therapeutic context of algR

• Sequence analysis around the algR gene revealed the absence of a fimS homolog [8].
• Electron microscopy of the cyst structures formed by the algR mutant revealed that the encystment process is blocked at the step of exine formation [8].
• Biological assays demonstrated that the algR mutant was significantly impaired in both pathogenicity and epiphytic fitness as compared to the wild-type strain [19].

References