Disease relevance of mucA

• The mucA gene of the muc operon, which is instrumental in the control of the biosynthesis of the exopolysaccharide alginate, is a hotspot of mutation in Pseudomonas aeruginosa, a micro-organism that chronically colonizes the airways of individuals with cystic fibrosis (CF) [1].
• Mucoid, mucA mutant Pseudomonas aeruginosa cause chronic lung infections in cystic fibrosis (CF) patients and are refractory to phagocytosis and antibiotics [2].
• The mutations in mucA result in the activation of the alternative sigma factor AlgU, the P. aeruginosa ortholog of Escherichia coli extreme stress sigma factor sigma(E) [3].
• Role of Azotobacter vinelandii mucA and mucC gene products in alginate production [4].
• This group of genes encodes AlgU, the P. aeruginosa equivalent of the extreme heat shock sigma factor sigma E in Gram-negative bacteria, the AlgU-cognate anti-sigma factor MucA, the periplasmic protein MucB and a serine protease homologue, MucD [5].

High impact information on mucA

• These results suggest that the switch from the nonmucoid to mucoid state can be caused by inactivation of mucA, resulting in constitutive expression of alginate biosynthetic genes dependent on algU for transcription and that such mutants may be selected in vivo during chronic infections in CF [6].
• The complete nucleotide sequence of mucA and mucB was determined [7].
• Both mucA and mucB play a regulatory role in concert with the sigma-like factor AlgU; all three genes, along with signal transduction and histone-like elements, control differentiation of P. aeruginosa into the mucoid phenotype [7].
• Nucleotide sequence analyses revealed that the majority of the alterations caused premature termination of the mucA coding sequence [8].
• Interestingly, mucoid P. aeruginosa isolates from urinary tract infections also had mutations in the mucA gene [8].

Biological context of mucA

• Results of reverse transcription-PCR demonstrated that algT, mucA, and mucB are cotranscribed as an operon in P. syringae [9].
• DeltaG430 was the most frequent and recurrent mucA mutation detected in four genotypes [1].
• In this work, we studied the transcriptional regulation of the A. vinelandii algU-mucABCD gene cluster, as well as the role of the mucA and mucC gene products in alginate production [4].
• Comparison of global gene expression of mucA mutant and wild-type PAK under T3SS-inducing conditions confirmed the down regulation of T3SS genes and up regulation of genes involved in alginate biosynthesis [10].
• We expressed and purified the protein products from the mucA and mucB open reading frames [11].

Anatomical context of mucA

• This gene cluster encodes an extreme stress response system composed of the ECF alternative sigma factor AlgU, the anti-sigma factor MucA located in the inner membrane and the negative regulator MucB located in the periplasm [12].

Other interactions of mucA

• The mucA, mucB and mucD genes were sequenced in nine environmental isolates from aquatic habitats, and in 37 P. aeruginosa strains isolated from 10 patients with CF, at onset or at a late stage of chronic airway colonization, in order to elucidate whether there was any association between mutation and background genotype [1].
• Moreover, insertional inactivation of either mucA or mucB resulted in further stimulation of transcriptional activity from the algD promoter [13].
• In the present study, the algT gene product from P. syringae pv. syringae showed 90% amino acid identity with its P. aeruginosa counterpart, and sequence analysis of the region flanking algT in P. syringae revealed the presence of nadB, mucA, and mucB in an arrangement virtually identical to that of P. aeruginosa [14].

Analytical, diagnostic and therapeutic context of mucA

• Sequence analysis of PCR products derived from the mucA gene showed 20 mutations, with the number of mutations in individual isolates ranging from 1 to 4; 19 of these changes are reported here for the first time [15].

References