Posttranslational Regulation of Antisigma Factors of RpoE: A Comparison Between the
            <i>escherichia Coli</i>
            and
            <i>Pseudomonas Aeruginosa</i>
            Systems

Pandey, Sundar; Martins, Kyle; Mathee, Kalai

doi:10.1002/9781119004813.ch32

Cited by 4 publications

(5 citation statements)

References 64 publications

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“…To further elucidate the regulatory cascade of alginate production, several precise in-frame deletions were constructed of the various players involved in MucA proteolysis. Although the specific signal that initiates the cascade that results in the mucoid phenotype has not been well characterized, MucA degradation occurs via RIP (20,25,28). This proteolytic cascade occurs in a manner similar to that of degradation of RseA in E. coli involved in the E stress response (20).…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa Regulated Intramembrane Proteolysis: Protease MucP Can Overcome Mutations in the AlgO Periplasmic Protease To Restore Alginate Production in Nonmucoid Revertants

et al. 2018

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The progression of cystic fibrosis (CF) from an acute to a chronic disease is often associated with the conversion of the opportunistic pathogen from a nonmucoid form to a mucoid form in the lung. This conversion involves the constitutive synthesis of the exopolysaccharide alginate, whose production is under the control of the AlgT/U sigma factor. This factor is regulated posttranslationally by an extremely unstable process and has been commonly attributed to mutations in the () gene. By exploiting this unstable phenotype, we isolated 34 spontaneous nonmucoid variants arising from the mucoid strain PDO300, a PAO1 derivative containing the allele commonly found in mucoid CF isolates. Complementation analysis using a minimal tiling path cosmid library revealed that most of these mutants mapped to two protease-encoding genes,, also known as or, and Interestingly, our mutations were complemented by both and, leading us to delete, clone, and overexpress ,, , and in both wild-type PAO1 and PDO300 backgrounds to better understand the regulation of this complex regulatory mechanism. Our findings suggest that the regulatory proteases follow two pathways for regulated intramembrane proteolysis (RIP), where both the AlgO/MucP pathway and MucE/AlgW pathway are required in the wild-type strain but where the AlgO/MucP pathway can bypass the MucE/AlgW pathway in mucoid strains with membrane-associated forms of MucA with shortened C termini, such as the MucA22 variant. This work gives us a better understanding of how alginate production is regulated in the clinically important mucoid variants of Infection by the opportunistic pathogen is the leading cause of morbidity and mortality seen in CF patients. Poor patient prognosis correlates with the genotypic and phenotypic change of the bacteria from a typical nonmucoid to a mucoid form in the CF lung, characterized by the overproduction of alginate. The expression of this exopolysaccharide is under the control an alternate sigma factor, AlgT/U, that is regulated posttranslationally by a series of proteases. A better understanding of this regulatory phenomenon will help in the development of therapies targeting alginate production, ultimately leading to an increase in the length and quality of life for those suffering from CF.

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Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa Regulated Intramembrane Proteolysis: Protease MucP Can Overcome Mutations in the AlgO Periplasmic Protease To Restore Alginate Production in Nonmucoid Revertants

et al. 2018

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“…Activation of the AlgU pathway occurs via RIP (reviewed in Damron and Goldberg, 2012), as does activation of the σ E pathway. In addition, Pseudomonas has functional equivalents of the E. coli proteases DegP, DegS and RseP; MucD, AlgW, and MucP, respectively (Pandey et al, 2016). Further to this, the ClpXP proteases are conserved in Pseudomonas and are required to release AlgU from MucA in the cytoplasm (Qiu et al, 2008).…”

Section: The Extracytoplasmic Sigma Factor σEmentioning

confidence: 99%

Maintaining Integrity Under Stress: Envelope Stress Response Regulation of Pathogenesis in Gram-Negative Bacteria

Cho

Rowley

Raivio

2019

Front. Cell. Infect. Microbiol.

118

129

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The Gram-negative bacterial envelope is an essential interface between the intracellular and harsh extracellular environment. Envelope stress responses (ESRs) are crucial to the maintenance of this barrier and function to detect and respond to perturbations in the envelope, caused by environmental stresses. Pathogenic bacteria are exposed to an array of challenging and stressful conditions during their lifecycle and, in particular, during infection of a host. As such, maintenance of envelope homeostasis is essential to their ability to successfully cause infection. This review will discuss our current understanding of the σE- and Cpx-regulated ESRs, with a specific focus on their role in the virulence of a number of model pathogens.

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“…Cleavage of MucA and MucB by AlgW in response to the dual stimuli. The MucA-RIP system is homologous to the E. coli RseA-RIP system (12). Correspondingly, AlgW, MucA, and MucB are analogous to DegS, RseA, and RseB, respectively.…”

Section: Resultsmentioning

confidence: 99%

Molecular Basis of the Versatile Regulatory Mechanism of HtrA-Type Protease AlgW from Pseudomonas aeruginosa

Song

Luo

et al. 2021

mBio

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AlgW, a membrane-bound periplasmic serine protease belonging to the HtrA protein family, is a key regulator of the regulated intramembrane proteolysis (RIP) pathway and is responsible for transmitting the envelope stress signals in Pseudomonas aeruginosa. The AlgW PDZ domain senses and binds the C-terminal of mis-localized outer membrane proteins (OMPs) or periplasmic protein MucE, leading to catalytic activation of the protease domain. While AlgW is functionally well studied, its exact activation mechanism remains to be elucidated. Here, we show that AlgW is a novel HtrA protease that can be biochemically activated by both peptide and lipid signals. Compared with the corresponding homologue DegS in Escherichia coli, AlgW exhibits a distinct substrate specificity and regulation mechanism. Structural, biochemical, and mutagenic analyses revealed that, by specifically binding to the C-terminal decapeptide of MucE, AlgW could adopt more relaxed conformation and obtain higher activity than with tripeptide activation. We also investigated the regulatory mechanism of the LA loop in AlgW and proved that the unique structural feature of this region was responsible for the distinct enzymatic property of AlgW. These results demonstrate the unique and diverse activation mechanism of AlgW, which P. aeruginosa may utilize to enhance its adaptability to environmental stress. IMPORTANCE HtrA-family proteases are commonly employed to sense the protein folding stress and activate the regulated intramembrane proteolysis (RIP) cascade in Gram-negative bacteria. Here, we reveal the unique dual-signal activation and dynamic regulation properties of AlgW, an HtrA-type protease triggering the AlgU stress-response pathway, which controls alginate production and mucoid conversion in Pseudomonas aeruginosa. The structural and functional data offer insights into the molecular basis underlying the transition of different activation states of AlgW in response to different effectors. Probing these unique features provides an opportunity to correlate the diverse regulation mechanism of AlgW with the high adaptability of P. aeruginosa to environmental changes during infection.

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Posttranslational Regulation of Antisigma Factors of RpoE: A Comparison Between the escherichia Coli and Pseudomonas Aeruginosa Systems

Cited by 4 publications

References 64 publications

Pseudomonas aeruginosa Regulated Intramembrane Proteolysis: Protease MucP Can Overcome Mutations in the AlgO Periplasmic Protease To Restore Alginate Production in Nonmucoid Revertants

Pseudomonas aeruginosa Regulated Intramembrane Proteolysis: Protease MucP Can Overcome Mutations in the AlgO Periplasmic Protease To Restore Alginate Production in Nonmucoid Revertants

Maintaining Integrity Under Stress: Envelope Stress Response Regulation of Pathogenesis in Gram-Negative Bacteria

Molecular Basis of the Versatile Regulatory Mechanism of HtrA-Type Protease AlgW from Pseudomonas aeruginosa

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