Overproduction of the AlgT sigma factor is lethal to mucoid<i>Pseudomonas aeruginosa</i>

Cross, Ashley R.; Raghuram, Vishnu; Wang, Zihuan; Dey, Debayan; Goldberg, Joanna B.

doi:10.1101/2020.06.05.136770

Cited by 2 publications

(2 citation statements)

References 58 publications

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“…Lastly, algU overexpression led to a growth defect, which was lethal at high levels in the absence of mucA (Figure 6), suggesting that high AlgU activity leads to cell death when MucA is not present. Overall, our work strongly suggests that mucA essentiality is caused by unchecked AlgU activity, in agreement with previous studies suggesting that overproduction of AlgU is toxic (Cross et al, 2020;Hershberger et al, 1995;Schurr et al, 1994).…”

Section: Discussionsupporting

confidence: 92%

The anti‐sigma factor MucA is required for viability in Pseudomonas aeruginosa

Schofield

Rodriguez

Kidman

et al. 2021

Molecular Microbiology

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The major cause of death in people with cystic fibrosis (CF), a human autosomal recessive genetic disease, is respiratory failure due to chronic lung infection. Pseudomonas aeruginosa is a prevalent CF respiratory pathogen (Cystic Fibrosis Foundation Patient Registry, 2019). The CF lung environment selects for mucoid P. aeruginosa mutants, which overproduce the exopolysaccharide alginate and are associated with poor disease prognosis (

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Section: Discussionsupporting

confidence: 92%

The anti‐sigma factor MucA is required for viability in Pseudomonas aeruginosa

Schofield

Rodriguez

Kidman

et al. 2021

Molecular Microbiology

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show abstract

“…Lastly, algU overexpression led to a growth defect, which was lethal at high levels in the absence of mucA (Fig 6), suggesting that high AlgU activity leads to cell death when MucA is not present. Overall, our work strongly suggests that mucA essentiality is caused by unchecked AlgU activity, in agreement with previous studies suggesting that overproduction of AlgU is toxic (Cross et al, 2020, Hershberger et al, 1995.…”

Section: Discussionsupporting

confidence: 92%

The anti-sigma factor MucA is required for viability inPseudomonas aeruginosa

Schofield

Rodriguez

Kidman

et al. 2020

Preprint

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Pseudomonas aeruginosa causes chronic lung infections in people with cystic fibrosis (CF), and this bacterium undergoes selection in the CF lung environment over the course of these life-long infections. One genetic adaptation frequently observed in CF P. aeruginosa isolates is mutation of mucA. MucA inhibits the sigma factor AlgU. Clinical mucA mutations lead to misregulation of AlgU, resulting in a mucoid bacterial phenotype that is associated with poor CF disease outcomes. Here we show that paradoxically a portion of the mucA gene is essential for P. aeruginosa viability. We demonstrate that mucA is no longer essential in a strain lacking algU, and mucA alleles that encode for proteins that do not bind to AlgU are insufficient for bacterial viability. Furthermore, we found that mucA is no longer essential in mutant strains containing AlgU variants with reduced sigma factor activity, suggesting that reducing AlgU activity can suppress the requirement for mucA. Finally, we found that overexpression of algU from an inducible promoter prevents cell growth in the absence of MucA, and that this phenotype can be rescued by overproduction of RpoD, the housekeeping sigma factor. Together, these results suggest that in the absence of MucA, the inability to regulate AlgU activity leads to sigma factor competition, preventing the expression of essential housekeeping genes and resulting in the loss of bacterial viability.

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Overproduction of the AlgT sigma factor is lethal to mucoidPseudomonas aeruginosa

Cited by 2 publications

References 58 publications

The anti‐sigma factor MucA is required for viability in Pseudomonas aeruginosa

The anti‐sigma factor MucA is required for viability in Pseudomonas aeruginosa

The anti-sigma factor MucA is required for viability inPseudomonas aeruginosa

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