Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width

ABSTRACT Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca2+-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. dams...

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Autores principales:	Gisela von Hoven, Amable J. Rivas, Claudia Neukirch, Martina Meyenburg, Qianqian Qin, Sapun Parekh, Nadja Hellmann, Matthias Husmann
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a4e4a71cfa2c4c41a7dc138fd91ececc
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spelling	oai:doaj.org-article:a4e4a71cfa2c4c41a7dc138fd91ececc2021-11-15T15:51:07ZRepair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width10.1128/mBio.02083-162150-7511https://doaj.org/article/a4e4a71cfa2c4c41a7dc138fd91ececc2017-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02083-16https://doaj.org/toc/2150-7511ABSTRACT Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca2+-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae. In striking contrast, Vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair. Mutational analysis uncovered a role of channel width in toxicity and repair. Thus, the replacement of serine at phobalysin´s presumed channel narrow point with the bulkier tryptophan, the corresponding residue in Vibrio cholerae cytolysin (W318), modulated Ca2+ influx, lysosomal exocytosis, and membrane repair. And yet, replacing tryptophan (W318) with serine in Vibrio cholerae cytolysin enhanced toxicity. The data reveal divergent strategies evolved by two related small β-pore-forming toxins to manipulate target cells: phobalysin leads to fulminant perturbation of ion concentrations, closely followed by Ca2+ influx-dependent membrane repair. In contrast, V. cholerae cytolysin causes insidious perturbations and escapes control by the cellular wounded membrane repair-like response. IMPORTANCE Previous studies demonstrated that large transmembrane pores, such as those formed by perforin or bacterial toxins of the cholesterol-dependent cytolysin family, trigger rapid, Ca2+ influx-dependent repair mechanisms. In contrast, recovery from attack by the small β-pore-forming Staphylococcus aureus alpha-toxin or aerolysin is slow in comparison and does not depend on extracellular Ca2+. To further elucidate the scope of Ca2+ influx-dependent repair and understand its limitations, we compared the cellular responses to phobalysin and V. cholerae cytolysin, two related small β-pore-forming toxins which create membrane pores of slightly different sizes. The data indicate that the channel width of a small β-pore-forming toxin is a critical determinant of both primary toxicity and susceptibility to Ca2+-dependent repair.Gisela von HovenAmable J. RivasClaudia NeukirchMartina MeyenburgQianqian QinSapun ParekhNadja HellmannMatthias HusmannAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 1 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Gisela von Hoven Amable J. Rivas Claudia Neukirch Martina Meyenburg Qianqian Qin Sapun Parekh Nadja Hellmann Matthias Husmann Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width
description	ABSTRACT Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca2+-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae. In striking contrast, Vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair. Mutational analysis uncovered a role of channel width in toxicity and repair. Thus, the replacement of serine at phobalysin´s presumed channel narrow point with the bulkier tryptophan, the corresponding residue in Vibrio cholerae cytolysin (W318), modulated Ca2+ influx, lysosomal exocytosis, and membrane repair. And yet, replacing tryptophan (W318) with serine in Vibrio cholerae cytolysin enhanced toxicity. The data reveal divergent strategies evolved by two related small β-pore-forming toxins to manipulate target cells: phobalysin leads to fulminant perturbation of ion concentrations, closely followed by Ca2+ influx-dependent membrane repair. In contrast, V. cholerae cytolysin causes insidious perturbations and escapes control by the cellular wounded membrane repair-like response. IMPORTANCE Previous studies demonstrated that large transmembrane pores, such as those formed by perforin or bacterial toxins of the cholesterol-dependent cytolysin family, trigger rapid, Ca2+ influx-dependent repair mechanisms. In contrast, recovery from attack by the small β-pore-forming Staphylococcus aureus alpha-toxin or aerolysin is slow in comparison and does not depend on extracellular Ca2+. To further elucidate the scope of Ca2+ influx-dependent repair and understand its limitations, we compared the cellular responses to phobalysin and V. cholerae cytolysin, two related small β-pore-forming toxins which create membrane pores of slightly different sizes. The data indicate that the channel width of a small β-pore-forming toxin is a critical determinant of both primary toxicity and susceptibility to Ca2+-dependent repair.
format	article
author	Gisela von Hoven Amable J. Rivas Claudia Neukirch Martina Meyenburg Qianqian Qin Sapun Parekh Nadja Hellmann Matthias Husmann
author_facet	Gisela von Hoven Amable J. Rivas Claudia Neukirch Martina Meyenburg Qianqian Qin Sapun Parekh Nadja Hellmann Matthias Husmann
author_sort	Gisela von Hoven
title	Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width
title_short	Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width
title_full	Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width
title_fullStr	Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width
title_full_unstemmed	Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width
title_sort	repair of a bacterial small β-barrel toxin pore depends on channel width
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/a4e4a71cfa2c4c41a7dc138fd91ececc
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Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width

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