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Pseudomonas Exotoxin A: optimized by evolution for effective killing.

Michalska M, Wolf P - Front Microbiol (2015)

Bottom Line: Pseudomonas Exotoxin A (PE) is the most toxic virulence factor of the pathogenic bacterium Pseudomonas aeruginosa.This review describes current knowledge about the intoxication pathways of PE.Moreover, PE represents a remarkable example for pathoadaptive evolution, how bacterial molecules have been structurally and functionally optimized under evolutionary pressure to effectively impair and kill their host cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Medical Center, University of Freiburg Freiburg, Germany.

ABSTRACT
Pseudomonas Exotoxin A (PE) is the most toxic virulence factor of the pathogenic bacterium Pseudomonas aeruginosa. This review describes current knowledge about the intoxication pathways of PE. Moreover, PE represents a remarkable example for pathoadaptive evolution, how bacterial molecules have been structurally and functionally optimized under evolutionary pressure to effectively impair and kill their host cells.

No MeSH data available.


(A) Schematic representation of the structural and functional domains of Pseudomonas Exotoxin A (PE). (B) Molecular pathways of PE. 2-KG, 2-ketogluconate; CCP, clathrin coated pit; CD91, CD91 receptor; CS, caveosome; EE, early endosome; eEF-2, eukaryotic elongation factor-2; ER, endoplasmatic reticulum; G, Golgi apparatus; KDEL-R, KDEL-receptor; PCP, plasma carboxypeptidases; PDI, protein disulfide isomerase; PtxR, PtxS, transcription regulators; R, ribosome; Rab, Rab-GTPase; RNA Pol, RNA polymerase; Sec61p, Sec61p translocon; T2SS, type II secretion system.
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Figure 1: (A) Schematic representation of the structural and functional domains of Pseudomonas Exotoxin A (PE). (B) Molecular pathways of PE. 2-KG, 2-ketogluconate; CCP, clathrin coated pit; CD91, CD91 receptor; CS, caveosome; EE, early endosome; eEF-2, eukaryotic elongation factor-2; ER, endoplasmatic reticulum; G, Golgi apparatus; KDEL-R, KDEL-receptor; PCP, plasma carboxypeptidases; PDI, protein disulfide isomerase; PtxR, PtxS, transcription regulators; R, ribosome; Rab, Rab-GTPase; RNA Pol, RNA polymerase; Sec61p, Sec61p translocon; T2SS, type II secretion system.

Mentions: A number of virulence factors enables P. aeruginosa to adhere to tissue surfaces, to damage tissue for dissemination and nutrition supply and to increase its survival rate (Coggan and Wolfgang, 2012; Jimenez et al., 2012; Balasubramanian et al., 2013). One of them is Pseudomonas Exotoxin A (PE), which has enzymatic activity and belongs to the mono-ADP-ribosyltransferase family (Liu, 1974). With regard to its function it is specified as NAD+-diphthamide-ADP-ribosyltransferase (EC 2.4.2.36) (Domenighini and Rappuoli, 1996). In the last years, the cytotoxic pathways of PE in eukaryotic host cells were investigated. Much relevant knowledge was obtained from studies with immunotoxins, in which the enzymatic active part of the toxin, coupled to antibodies, antibody fragments or ligands, was used for targeted therapeutic approaches against different cancers. Preclinical and clinical trials with PE-based immunotoxins were reviewed elsewhere (Wolf and Elsasser-Beile, 2009; Weidle et al., 2014). In the present article, we describe the cytotoxic pathways of PE (Figure 1) and how this molecule was structurally and functionally optimized under evolutionary pressure to effectively impair and finally kill its host cells.


Pseudomonas Exotoxin A: optimized by evolution for effective killing.

Michalska M, Wolf P - Front Microbiol (2015)

(A) Schematic representation of the structural and functional domains of Pseudomonas Exotoxin A (PE). (B) Molecular pathways of PE. 2-KG, 2-ketogluconate; CCP, clathrin coated pit; CD91, CD91 receptor; CS, caveosome; EE, early endosome; eEF-2, eukaryotic elongation factor-2; ER, endoplasmatic reticulum; G, Golgi apparatus; KDEL-R, KDEL-receptor; PCP, plasma carboxypeptidases; PDI, protein disulfide isomerase; PtxR, PtxS, transcription regulators; R, ribosome; Rab, Rab-GTPase; RNA Pol, RNA polymerase; Sec61p, Sec61p translocon; T2SS, type II secretion system.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4584936&req=5

Figure 1: (A) Schematic representation of the structural and functional domains of Pseudomonas Exotoxin A (PE). (B) Molecular pathways of PE. 2-KG, 2-ketogluconate; CCP, clathrin coated pit; CD91, CD91 receptor; CS, caveosome; EE, early endosome; eEF-2, eukaryotic elongation factor-2; ER, endoplasmatic reticulum; G, Golgi apparatus; KDEL-R, KDEL-receptor; PCP, plasma carboxypeptidases; PDI, protein disulfide isomerase; PtxR, PtxS, transcription regulators; R, ribosome; Rab, Rab-GTPase; RNA Pol, RNA polymerase; Sec61p, Sec61p translocon; T2SS, type II secretion system.
Mentions: A number of virulence factors enables P. aeruginosa to adhere to tissue surfaces, to damage tissue for dissemination and nutrition supply and to increase its survival rate (Coggan and Wolfgang, 2012; Jimenez et al., 2012; Balasubramanian et al., 2013). One of them is Pseudomonas Exotoxin A (PE), which has enzymatic activity and belongs to the mono-ADP-ribosyltransferase family (Liu, 1974). With regard to its function it is specified as NAD+-diphthamide-ADP-ribosyltransferase (EC 2.4.2.36) (Domenighini and Rappuoli, 1996). In the last years, the cytotoxic pathways of PE in eukaryotic host cells were investigated. Much relevant knowledge was obtained from studies with immunotoxins, in which the enzymatic active part of the toxin, coupled to antibodies, antibody fragments or ligands, was used for targeted therapeutic approaches against different cancers. Preclinical and clinical trials with PE-based immunotoxins were reviewed elsewhere (Wolf and Elsasser-Beile, 2009; Weidle et al., 2014). In the present article, we describe the cytotoxic pathways of PE (Figure 1) and how this molecule was structurally and functionally optimized under evolutionary pressure to effectively impair and finally kill its host cells.

Bottom Line: Pseudomonas Exotoxin A (PE) is the most toxic virulence factor of the pathogenic bacterium Pseudomonas aeruginosa.This review describes current knowledge about the intoxication pathways of PE.Moreover, PE represents a remarkable example for pathoadaptive evolution, how bacterial molecules have been structurally and functionally optimized under evolutionary pressure to effectively impair and kill their host cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Medical Center, University of Freiburg Freiburg, Germany.

ABSTRACT
Pseudomonas Exotoxin A (PE) is the most toxic virulence factor of the pathogenic bacterium Pseudomonas aeruginosa. This review describes current knowledge about the intoxication pathways of PE. Moreover, PE represents a remarkable example for pathoadaptive evolution, how bacterial molecules have been structurally and functionally optimized under evolutionary pressure to effectively impair and kill their host cells.

No MeSH data available.