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Bacterial Pore-Forming Toxin in Macromolecule Delivery: Lessons Learned from Listeriolysin O

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Microbial Toxins

Part of the book series: Toxinology ((TOXI))

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Abstract

Listeriolysin O (LLO) is a pore-forming hemolytic toxin, secreted by the Gram-positive pathogen Listeria monocytogenes (LM), responsible for bacterial phagosome escape into the cytosol of an infected host cell and spreading infection. The unique pore-forming ability of LLO has been widely studied to expand our understanding of the host–pathogen interaction, virulence factors, biochemical and signaling events, and modification of host cell membrane leading to pore formation. These elegant studies delineated a clever survival mechanism adopted by this pathogen, that can seemingly be exploited to deliver macromolecules in human antigen-presenting cells (APCs) targeting a specific pathway of antigen processing and presentation to a subset of T lymphocytes. Cytotoxic T lymphocytes (CTLs) protect us against extracellular pathogen infection and cancer by recognizing peptide antigens derived from cytosolic processing and the presentation pathway. It is a daunting task to deliver biologic macromolecules, such as protein or nucleic acid antigen, to prime a CTL response due to the membrane impermeable nature of these macromolecules. In this chapter, different areas of biotechnology applications of LLO as a pH-sensitive, membrane pore-forming hemolysin will be reviewed in the context of novel vaccine delivery strategies to intracellular pathogens, tumor antigens, or DNA.

Dedication: Author wishes to dedicate this chapter in loving memory of his late father, Dr. D. D. Mandal, who remains his life-long inspiration in science.

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Acknowledgments

The author acknowledges listeriolysin O-related research opportunity provided by K.D. Lee, University of Michigan College of Pharmacy. Grant support is provided by UM, NIH funding to K.D. Lee and Upjohn Vahlteich research award to M. Mandal.

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Authors and Affiliations

  1. College of Pharmacy, Roseman University of Health Sciences, 11 Sunset Way, Henderson, NV, 89014, USA

    Manas Mandal

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  1. Manas Mandal
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Correspondence to Manas Mandal .

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Editors and Affiliations

  1. Biology Department, Wilson College, Chambersburg, Pennsylvania, USA

    Brad Stiles

  2. Department of Biochemistry, School of Medicine and Instituto Clodomiro Picado, Faculty of Microbiology, University of Costa Rica, San Pedro de Montes de Oca, Costa Rica

    Alberto Alape-Girón

  3. Department of Pathology and Microbiology, Université de Montréal, Saint-Hyacinthe, Québec, Canada

    J. Daniel Dubreuil

  4. College of Pharmacy, Roseman University of Health Sciences, Henderson, Nevada, USA

    Manas Mandal

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Mandal, M. (2018). Bacterial Pore-Forming Toxin in Macromolecule Delivery: Lessons Learned from Listeriolysin O. In: Stiles, B., Alape-Girón, A., Dubreuil, J., Mandal, M. (eds) Microbial Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6449-1_20

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