Local and Global Regulators Linking Anaerobiosis tocupAFimbrial Gene Expression inPseudomonas aeruginosa

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Abstract
ThecupAgene cluster ofPseudomonas aeruginosaencodes components and assembly factors of a putative fimbrial structure that enable this opportunistic pathogen to form biofilms on abiotic surfaces. InP. aeruginosathe control ofcupAgene expression is complex, with the H-NS-like MvaT protein functioning to repress phase-variable (on/off) expression of the operon. Here we identify four positive regulators ofcupAgene expression, including three unusual regulators encoded by thecgrABCgenes and Anr, a global regulator of anaerobic gene expression. We show that thecupAgenes are expressed in a phase-variable manner under anaerobic conditions and that thecgrgenes are essential for this expression. We show further thatcgrgene expression is negatively controlled by MvaT and positively controlled by Anr and anaerobiosis. Expression of thecupAgenes therefore appears to involve a regulatory cascade in which anaerobiosis, signaled through Anr, stimulates expression of thecgrgenes, resulting in a concomitant increase incupAgene expression. Our findings thus provide mechanistic insight into the regulation ofcupAgene expression and identify anaerobiosis as an inducer of phase-variablecupAgene expression, raising the possibility that phase-variable expression of fimbrial genes important for biofilm formation may occur inP. aeruginosapersisting in the largely anaerobic environment of the cystic fibrosis host lung.

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