Disease relevance of algC

• Avirulence of a Pseudomonas aeruginosa algC mutant in a burned-mouse model of infection [1].
• Defined mutants derived from strain PAO i.e., PAOR1 (lasR),PAO-pmm (algC) (an LPS mutant), and AK1152 (which is Fla- and lacks functional pili), were significantly less virulent than PAO1 in a BALBc/ByJ neonatal mouse model of infection as measured by their abilities to cause acute pneumonia, bacteremia, and death [2].
• Alginate biosynthetic activity was determined with a mucoid cell line derived from a cystic fibrosis isolate and containing an alginate algC promoter fused to a lacZ reporter gene [3].

High impact information on algC

• The upstream region of the algC gene contained a sequence identical to the algD upstream sequence that is known to be the binding site for the AlgR1 protein [4].
• The nucleotide sequence of the Pseudomonas aeruginosa algC gene encoding phosphomannomutase (PMM; EC 5.4.2.8) was determined [4].
• DNA sequence analysis of a defective algC gene (algC') cloned from a mutant of P. aeruginosa that lacked PMM activity revealed one point mutation (a C to T transition) in the carboxyl terminus of PMM which resulted in an amino acid change from arginine 420 to cysteine 420 [4].
• Lipopolysaccharide was not a potent stimulus of cytokine expression, and P. aeruginosa algC (lipopolysaccharide) and lasR (quorum sensing) mutants were fully capable of activating epithelial cells [5].
• Additionally, AlgR controls transcription of algC, encoding a dual-function enzyme necessary for both lipopolysaccharide (LPS) and alginate production [6].

Chemical compound and disease context of algC

• The algC gene from Pseudomonas aeruginosa has been shown to encode phosphomannomutase (PMM), an essential enzyme for biosynthesis of alginate and lipopolysaccharide (LPS) [7].
• Pattern of changes in the activity of enzymes of GDP-D-mannuronic acid synthesis and in the level of transcription of algA, algC and algD genes accompanying the loss and emergence of mucoidy in Pseudomonas aeruginosa [8].

Biological context of algC

• The virulence of wild-type Pseudomonas aeruginosa PAO1 and that of a genetically defined algC mutant, PAO1 algC::tet, were compared in a burned-mouse model of infection [1].
• This same size restriction fragment contains the alginate gene algC, which encodes the enzyme phosphomannomutase (PMM) and also maps to this region of the P. aeruginosa chromosome [9].
• In addition, the cloned gene could complement the PMM deficiency in the algC mutant strain 8858, and the cloned algC gene could restore the LPS-smooth phenotype to strain AK1012 [9].
• Phosphorylation of the AlgR1 protein resulted in the stimulation of its in vitro ability to bind to the algC promoter region (a fragment spanning nucleotides -378 to -73) [10].
• In both mucoid (alginate-positive) and nonmucoid (alginate-negative) P. aeruginosa strains, transcriptional activation of algC increased with the osmolarity of the culture medium [10].

Associations of algC with chemical compounds

• We have previously shown that the P. aeruginosa algC gene is required for biosynthesis of alginate and lipopolysaccharide (M.J. Coyne, Jr., K.S. Russell, C.L. Coyle, and J.B. Goldberg, J. Bacteriol. 176:3500-3507, 1994) [1].
• Our finding that the algC gene product has PGM activity and that strains with mutations in this gene produce a truncated LPS core suggests that the synthesis of glucose 1-phosphate is necessary in the biosynthesis of the P. aeruginosa LPS core [11].
• Alginate biosynthesis begins with the formation of an activated monomer, GDP-mannuronate, which is known to occur via the products of the algA, algC, and algD genes [12].

Other interactions of algC

• Transcription from the algC promoter, which has significant homology with the RNA polymerase sigma-54 (RpoN) recognition sequence, decreased in an rpoN mutant of P. aeruginosa [10].
• Nevertheless, no transcripts homologous to algA (encoding a bifunctional enzyme that possesses both PMI and GMP activities) were detected in the nonmucoid form, and the levels of algC (encoding PMM) transcripts, although detectable in the nonmucoid variants, were, in general, much higher in the mucoid forms [8].

Analytical, diagnostic and therapeutic context of algC

• Deletion mapping, in conjunction with mobility shift assays, showed that AlgR1 specifically bound with two regions of algC upstream DNA [10].
• In the current study, the algC promoter region was cloned from P. syringae pv. syringae strain FF5, and sequence analysis of the algC promoter indicated the presence of potential binding sites for AlgR and sigma(54), the alternative sigma factor encoded by rpoN [13].

References