ExsD is a negative regulator of the <i>Pseudomonas aeruginosa</i> type III secretion regulon

McCaw, Michelle L.; Lykken, Guinevere L.; Singh, Pradeep Kumar; Yahr, Timothy L.

doi:10.1046/j.1365-2958.2002.03228.x

Cited by 148 publications

(271 citation statements)

References 46 publications

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“…ExsD is an anti-activator that binds to and inhibits ExsA-dependent transcription ( Fig. 2A) [29]. ExsC functions as an anti-anti-activator by binding to and inhibiting the negative regulatory activity of ExsD [30].…”

Section: Pseudomonas Aeruginosamentioning

confidence: 99%

Control of gene expression by type III secretory activity

Brutinel

Yahr

2008

Current Opinion in Microbiology

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SummaryThe bacterial flagellum and the highly related injectisome (or needle complex) are among the most complicated multi-protein structures found in Gram-negative microorganisms. The assembly of both structures is dependent upon a type III secretion system. An interesting regulatory feature unique to these systems is the coordination of gene expression with type III secretory activity. This means of regulation ensures that secretion substrates are expressed only when required during the assembly process or upon completion of the fully functional structure. Prominent within the regulatory scheme are secreted proteins and type III secretion chaperones that exert effects on gene expression at the transcriptional and post-transcriptional levels. Although the major structural components of the flagellum and injectisome systems are highly conserved, recent studies reveal diversity in the mechanisms used by secretion substrates and chaperones to control gene expression.

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Section: Pseudomonas Aeruginosamentioning

confidence: 99%

Control of gene expression by type III secretory activity

Brutinel

Yahr

2008

Current Opinion in Microbiology

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“…high levels of expression and secretion are seen, irrespective of the Ca 2+ concentration (Forsberg et al, 1991;Nilles et al, 1997;Day & Plano, 1998;Cheng & Schneewind, 2000;Matson & Nilles, 2001). Differing from the genus Yersinia, mutation in the pcrV gene of P. aeruginosa has been shown to result in constitutive secretion of type III effector molecules (Sawa et al, 1999;McCaw et al, 2002). However, no interactions between PcrV and the identified TSF molecules were observed (J. Kim & S. Jin, unpublished results), suggesting alternative target molecules for the TSF.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, a number of genes have been shown to affect the expression of type III genes, including adenylcyclase (cyaA), pseudouridinase (truA) and pyruvate dehydrogenase (aceAB) (Dacheux et al, 2002;Wolfgang et al, 2003;Ahn et al, 2004). Meanwhile, the type III genes are also regulated negatively by ExsD, the RhlI/RhlR quorum-sensing system and stationary-phase sigma factor RpoS (McCaw et al, 2002;Hogardt et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Factors triggering type III secretion in Pseudomonas aeruginosa

et al. 2005

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The type III secretion system of Pseudomonas aeruginosa is tightly regulated by various environmental signals, such as low calcium and contact with the host cell. However, the exact signals triggering type III secretion are unknown. The present study describes the finding that secretion of P. aeruginosa type III effector molecules requires protein factors from serum and L broth, designated type III secretion factors (TSFs), in addition to the low-calcium environment. In the absence of TSF or calcium chelator EGTA, basal levels of type III effector molecules are accumulated intracellularly. Addition of TSF and EGTA together effectively triggers the secretion of pre-existing effector molecules in a short time, even before the active expression of type III genes; thus, active type III gene expression does not seem to be a prerequisite for type III secretion. A search for TSF molecules in serum and L broth resulted in the identification of albumin and casein as the functional TSF molecules. Although there is no clear sequence similarity between albumin and casein, both proteins are known to have a low-affinity, high-capacity calcium-binding property. Tests of well-studied calcium-binding proteins seemed to indicate that low-affinity calcium-binding proteins have TSF activity, although the requirement of low-affinity calcium-binding ability for the TSF activity is not clear. P. aeruginosa seems to have evolved a sensing mechanism to detect target cells for type III injection through host-derived proteins in combination with a low-calcium signal. Disruption of the bacterial ability to sense low calcium or TSF might be a valid avenue to the effective control of this bacterial pathogen. INTRODUCTIONThe remarkable ability of Pseudomonas aeruginosa to adapt to and thrive in a wide variety of environments contributes significantly to the ability of this bacterium to cause various human infections (Bodey et al., 1983;Holder, 1993;Pier, 2002). Unlike most human pathogens possessing highly restricted host ranges, P. aeruginosa is pathogenic not only to humans, but also to Caenorhabditis elegans, Drosophila and Arabidopsis thaliana (Rahme et al., 1995;D'Argenio et al., 2001;Aballay & Ausubel, 2002). This broad host range is contributed in part by the numerous virulence factors encoded by P. aeruginosa, including exotoxin A, phospholipase C, alkaline protease, elastase, alginate, pyocyanin, pili and non-pilus adhesins (Ramphal et al., 1991;Deretic et al., 1995;Lory & Strom, 1997;Vasil & Ochsner, 1999). P. aeruginosa, like many other Gram-negative animal and plant pathogens, also encodes a type III secretion machinery, where over 30 proteins assemble into a complex designed to deliver effector molecules directly into the cytoplasmic compartment of eukaryotic cells (Yahr et al., 1995;Frank, 1997). Injection of the bacterial effector molecules into the host cells results in various physiological changes, all of which seem to confer a survival advantage on the bacterial pathogen within the host environment (Hueck, 1998;Muller et al...

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“…The first gene exsD of one of the operons regulated by ExsA, encodes an inhibitor of ExsA. (McCaw et al, 2002) (Figure 2a). Two feedback circuits thus control ExsA, a positive feedback circuit at the transcriptional level and a negative feedback circuit involving the activity of ExsA.…”

Section: Cytotoxicitymentioning

confidence: 99%

Epigenesis and Dynamic Similarity in Two Regulatory Networks in Pseudomonas Aeruginosa

et al. 2004

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Mucoidy and cytotoxicity arise from two independent modifications of the phenotype of the bacterium Pseudomonas aeruginosa that contribute to the mortality and morbidity of cystic fibrosis. We show that, even though the transcriptional regulatory networks controlling both processes are quite different from a molecular or mechanistic point of view, they may be identical from a dynamic point of view: epigenesis may in both cases be the cause of the acquisition of these new phenotypes. This was highlighted by the identity of formal graphs modelling these networks. A mathematical framework based on formal methods from computer science was defined and implemented with a software environment. It allows an easy and rigorous validation and certification of these models and of the experimental methods that can be proposed to falsify or validate the underlying hypothesis.

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ExsD is a negative regulator of the Pseudomonas aeruginosa type III secretion regulon

Cited by 148 publications

References 46 publications

Control of gene expression by type III secretory activity

Control of gene expression by type III secretory activity

Factors triggering type III secretion in Pseudomonas aeruginosa

Epigenesis and Dynamic Similarity in Two Regulatory Networks in Pseudomonas Aeruginosa

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