Control of AlgU, a member of the sigma E-like family of stress sigma factors, by the negative regulators MucA and MucB and Pseudomonas aeruginosa conversion to mucoidy in cystic fibrosis.
The alternative sigma factor AlgU (Pseudomonas aeruginosa sigma E) is required for full resistance of P. aeruginosa to oxidative stress and extreme temperatures. AlgU also controls conversion of P. aeruginosa to the mucoid, alginate-overproducing phenotype associated with lethal infections in cystic fibrosis patients. Mutations that cause conversion to mucoidy in cystic fibrosis isolates occur frequently in mucA, the second gene within the algU mucABCD gene cluster. Here we analyze the biochemical basis of conversion to mucoidy. MucA was shown to act as an anti-sigma factor by binding to AlgU and inhibiting its activity. MucB, another negative regulator of AlgU, was localized in the periplasm. MucB exerts its function from this compartment, since deletion of the leader peptide and the cytoplasmic location of MucB abrogated its ability to inhibit mucoidy. These data support a model in which a multicomponent system, encompassing an anti-delta factor and elements in the periplasmic compartment, modulates activity of AlgU. Since factors controlling AlgU are conserved in other gram-negative bacteria, the processes controlling conversion to mucoidy in P. aeruginosa may be applicable to the regulation of AlgU (sigma E) equivalents in other organisms.
Schurr
M J
MJ
Department of Microbiology, University of Texas Health Science Center at San Antonio 78284-7758, USA.
Yu
H
H
Martinez-Salazar
J M
JM
Boucher
J C
JC
Deretic
V
V
D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001483:Base Sequence; D002874:Chromosome Mapping; D003550:Cystic Fibrosis / Q000150:complications* / Q000382:microbiology; D017931:DNA Primers; D004926:Escherichia coli; D005785:Gene Conversion; D005798:Genes, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D018384:Oxidative Stress; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D012808:Sigma Factor / Q000378:metabolism*; D013696:Temperature; D014157:Transcription Factors; D014158:Transcription, Genetic
C079619:AlgU protein, Pseudomonas aeruginosa; D001426:Bacterial Proteins; D017931:DNA Primers; C063757:MucA protein, Bacteria; C093590:MucB protein, Bacteria; D011993:Recombinant Fusion Proteins; D012808:Sigma Factor; D014157:Transcription Factors