Pseudomonas Exotoxin A: optimized by evolution for effective killing

Michalska, Marta; Wolf, Philipp

doi:10.3389/fmicb.2015.00963

Cited by 208 publications

(168 citation statements)

References 63 publications

(76 reference statements)

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“…The regulation of ETA is complex and related to glucose and iron metabolism and the Las/Rhl circuits of the QS system (Fig. 1) [58]. …”

Section: Qs-regulated Factors That Impact P Aeruginosa Communities Amentioning

confidence: 99%

Bacteria-Host Crosstalk: Sensing of the Quorum in the Context of Pseudomonas aeruginosa Infections

Turkina

Vikström

2018

J Innate Immun

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Cell-to-cell signaling via small molecules is an essential process to coordinate behavior in single species within a community, and also across kingdoms. In this review, we discuss the quorum sensing (QS) systems used by the opportunistic pathogen Pseudomonas aeruginosa to sense bacterial population density and fitness, and regulate virulence, biofilm development, metabolite acquisition, and mammalian host defense. We also focus on the role of N-acylhomoserine lactone-dependent QS signaling in the modulation of innate immune responses connected together via calcium signaling, homeostasis, mitochondrial and cytoskeletal dynamics, and governing transcriptional and proteomic responses of host cells. A future perspective emphasizes the need for multidisciplinary efforts to bring current knowledge of QS into a more detailed understanding of the communication between bacteria and host, as well as into strategies to prevent and treat P. aeruginosa infections and reduce the rate of antibiotic resistance.

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“…The regulation of ETA is complex and related to glucose and iron metabolism and the Las/Rhl circuits of the QS system (Fig. 1) [58]. …”

Section: Qs-regulated Factors That Impact P Aeruginosa Communities Amentioning

confidence: 99%

Bacteria-Host Crosstalk: Sensing of the Quorum in the Context of Pseudomonas aeruginosa Infections

Turkina

Vikström

2018

J Innate Immun

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“…Domain II, designated as the transmembrane domain, is responsible for permeabilization through cellular membranes and cytosolic localization. Domains Ib and III cause ADPribosylation of the elongation factor 2 (eEF2) on the ribosomes, resulting in inhibition of protein biosynthesis and effective cell death (10).…”

mentioning

confidence: 99%

In Vitro Evaluation of Humanized/De-immunized Anti-PSMA Immunotoxins for the Treatment of Prostate Cancer

Michalska

Schultze-Seemann

Kuckuck

et al. 2018

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“…Domain III has been studied the most and was found to be responsible for the catalytic activity of the toxin [23,24,25]. This domain inhibits protein synthesis by modifying elongation factor 2 through ADP-Ribosylation [24,26,27]. The blocking of protein synthesis can lead to the initiation of apoptotic death in cancer cells [24,26].…”

Section: Introductionmentioning

confidence: 99%

“…This domain inhibits protein synthesis by modifying elongation factor 2 through ADP-Ribosylation [24,26,27]. The blocking of protein synthesis can lead to the initiation of apoptotic death in cancer cells [24,26]. The C-terminal amino acid sequence in domain III is thought to play a role in retrograde targeting of the toxin from the Golgi apparatus to the endoplasmic reticulum.…”

Section: Introductionmentioning

confidence: 99%

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Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer

Fleming

2016

Toxins

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Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, yet no effective therapeutics exist. This review provides an overview of the recent development of recombinant immunotoxins for the treatment of glypican-3 (GPC3) expressing HCC. GPC3 is a cell surface heparan sulfate proteoglycan that is overexpressed in HCC, but is absent from normal adult human tissues. Treatment of HCC with anti-GPC3 immunotoxins represents a new therapeutic option. Using phage display and hybridoma technologies, three high affinity antibodies (HN3, HS20 and YP7) have been generated against GPC3. Two of these antibodies (HN3 and HS20) have demonstrated the ability to inhibit Wnt/Yap signaling, leading to a reduction in liver cancer cell proliferation. By combining the HN3 antibody capable of inhibiting Wnt/Yap signaling with the protein synthesis inhibitory domain of the Pseudomonas exotoxin, a recombinant immunotoxin that exhibits a dual inhibitory mechanism was generated. This immunotoxin was found to be highly effective in the treatment of human HCCs in mouse xenograft models. Engineering of the toxin fragment to reduce the level of immunogenicity is currently being explored. The development of immunotoxins provides opportunities for novel liver cancer therapies.

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Pseudomonas Exotoxin A: optimized by evolution for effective killing

Cited by 208 publications

References 63 publications

Bacteria-Host Crosstalk: Sensing of the Quorum in the Context of <b><i>Pseudomonas aeruginosa</i></b> Infections

Bacteria-Host Crosstalk: Sensing of the Quorum in the Context of <b><i>Pseudomonas aeruginosa</i></b> Infections

In Vitro Evaluation of Humanized/De-immunized Anti-PSMA Immunotoxins for the Treatment of Prostate Cancer

Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer

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