Advances in Bacterial Toxin-Based Platforms

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Nanotechnology Applications in Bioengineering".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 3729

Special Issue Editor


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Guest Editor
1. Department of Urology, Boston Children’s Hospital, Boston, MA, USA
2. Department of Microbiology, Harvard Medical School, Boston, MA, USA
Interests: bacterial toxin; toxin biology; receptor; host factor; host-pathogen interactions; genetic screen; CRISPR; toxin engineering; immunotoxin

Special Issue Information

Dear Colleagues,

As a type of virulence factor, bacterial toxins are evolved protein nanomachines used to target, enter, and modulate key biological processes in the host cells. Once being produced and released, these nanomachines autonomously play a role as “guide missiles”, targeting the host cells via recognizing specific cellular receptors. Some, including pore-forming toxins, act directly on the plasma membrane. The most dangerous ones enter the cell through multiple routes and act on their intracellular substrates. These multiple-step mechanisms of action for toxins are achieved with specialized domain arrangement in an ‘‘AB’’ paradigm, with the A domain as the enzymatic cargo and the B domain as a delivery tool composed of the receptor-binding domain and membrane translocation domain.

These naturally evolved properties of toxins provide a powerful toolbox for engineering and developing toxin-based platforms to target specific cells/tissues and achieve intracellular delivering of protein cargoes. In the last few decades, many of these toxins have been explored along this line. Examples are diphtheria toxin (DT), botulinum neurotoxins (BoNTs), anthrax toxin (AT), pseudomonas exotoxin A (PE), alpha hemolysin (αHL), tripartite toxin complexes (Tc), shiga toxin (Stx), and cholera toxin (Ctx).

The Special Issue, titled "Advances in Bacterial Toxin-Based Platforms", will highlight the recent innovations and developments in the engineering of bacterial toxin-based platforms for multiple applications. I would like to invite colleagues to contribute both reviews and original articles within the scope of this Special Issue. The potential topics may include, but are not limited to, toxin-based delivery systems, immunotoxins, toxin-based probes, Botox, anticancer toxins and/or toxin fragments, and pore-forming toxin-based nanopore sequencing.

I look forward to receiving your contributions for this Special Issue.

Dr. Songhai Tian
Guest Editor

Manuscript Submission Information

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Keywords

  • bacterial toxin
  • toxin biology
  • toxin receptor
  • endosomal trafficking
  • toxin engineering
  • intracellular delivery
  • immunotoxin
  • nanopore sequencing

Published Papers (2 papers)

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Review

27 pages, 7090 KiB  
Review
Gaining New Insights into Fundamental Biological Pathways by Bacterial Toxin-Based Genetic Screens
by Songhai Tian and Nini Zhou
Bioengineering 2023, 10(8), 884; https://doi.org/10.3390/bioengineering10080884 - 25 Jul 2023
Viewed by 1597
Abstract
Genetic screen technology has been applied to study the mechanism of action of bacterial toxins—a special class of virulence factors that contribute to the pathogenesis caused by bacterial infections. These screens aim to identify host factors that directly or indirectly facilitate toxin intoxication. [...] Read more.
Genetic screen technology has been applied to study the mechanism of action of bacterial toxins—a special class of virulence factors that contribute to the pathogenesis caused by bacterial infections. These screens aim to identify host factors that directly or indirectly facilitate toxin intoxication. Additionally, specific properties of certain toxins, such as membrane interaction, retrograde trafficking, and carbohydrate binding, provide robust probes to comprehensively investigate the lipid biosynthesis, membrane vesicle transport, and glycosylation pathways, respectively. This review specifically focuses on recent representative toxin-based genetic screens that have identified new players involved in and provided new insights into fundamental biological pathways, such as glycosphingolipid biosynthesis, protein glycosylation, and membrane vesicle trafficking pathways. Functionally characterizing these newly identified factors not only expands our current understanding of toxin biology but also enables a deeper comprehension of fundamental biological questions. Consequently, it stimulates the development of new therapeutic approaches targeting both bacterial infectious diseases and genetic disorders with defects in these factors and pathways. Full article
(This article belongs to the Special Issue Advances in Bacterial Toxin-Based Platforms)
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16 pages, 1974 KiB  
Review
Cancer Drug Delivery Systems Using Bacterial Toxin Translocation Mechanisms
by Linxiang Yin and Hatim Thaker
Bioengineering 2023, 10(7), 813; https://doi.org/10.3390/bioengineering10070813 - 07 Jul 2023
Cited by 1 | Viewed by 1690
Abstract
Recent advances in targeted cancer therapy hold great promise for both research and clinical applications and push the boundaries in finding new treatments for various currently incurable cancers. However, these therapies require specific cell-targeting mechanisms for the efficient delivery of drug cargo across [...] Read more.
Recent advances in targeted cancer therapy hold great promise for both research and clinical applications and push the boundaries in finding new treatments for various currently incurable cancers. However, these therapies require specific cell-targeting mechanisms for the efficient delivery of drug cargo across the cell membrane to reach intracellular targets and avoid diffusion to unwanted tissues. Traditional drug delivery systems suffer from a limited ability to travel across the barriers posed by cell membranes and, therefore, there is a need for high doses, which are associated with adverse reactions and safety concerns. Bacterial toxins have evolved naturally to specifically target cell subtypes via their receptor binding module, penetrating the cell membrane efficiently through the membrane translocation process and then successfully delivering the toxic cargo into the host cytosol. They have, thus, been harnessed for the delivery of various drugs. In this review, we focus on bacterial toxin translocation mechanisms and recent progress in the targeted delivery systems of cancer therapy drugs that have been inspired by the receptor binding and membrane translocation processes of the anthrax toxin protective antigen, diphtheria toxin, and Pseudomonas exotoxin A. We also discuss the challenges and limitations of these studies that should be addressed before bacterial toxin-based drug delivery systems can become a viable new generation of drug delivery approaches in clinical translation. Full article
(This article belongs to the Special Issue Advances in Bacterial Toxin-Based Platforms)
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