Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity

The respiratory tract is a major entry site for microbial pathogens. To combat bacterial infections, the immune system has various defense mechanisms at its disposal, including antimicrobial peptides (AMPs). To search for novel AMPs from the respiratory tract, a peptide library from human broncho-al...

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Autores principales:	Armin Holch, Richard Bauer, Lia-Raluca Olari, Armando A. Rodriguez, Ludger Ständker, Nico Preising, Merve Karacan, Sebastian Wiese, Paul Walther, Yasser B. Ruiz-Blanco, Elsa Sanchez-Garcia, Christian Schumann, Jan Münch, Barbara Spellerberg
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	ß2-microglobulin antimicrobial peptides innate immunity ph amyloid Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/f10bbf2e1585497dbe0729aeccdbea55
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spelling	oai:doaj.org-article:f10bbf2e1585497dbe0729aeccdbea552021-11-17T14:21:59ZRespiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity2150-55942150-560810.1080/21505594.2020.1831367https://doaj.org/article/f10bbf2e1585497dbe0729aeccdbea552020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1831367https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608The respiratory tract is a major entry site for microbial pathogens. To combat bacterial infections, the immune system has various defense mechanisms at its disposal, including antimicrobial peptides (AMPs). To search for novel AMPs from the respiratory tract, a peptide library from human broncho-alveolar-lavage (BAL) fluid was screened for antimicrobial activity by radial diffusion assays allowing the efficient detection of antibacterial activity within a small sample size. After repeated testing-cycles and subsequent purification, we identified ß-2-microglobulin (B2M) in antibacterially active fractions. B2M belongs to the MHC-1 receptor complex present at the surface of nucleated cells. It is known to inhibit the growth of Listeria monocytogenes and Escherichia coli and to facilitate phagocytosis of Staphylococcus aureus. Using commercially available B2M we confirmed a dose-dependent inhibition of Pseudomonas aeruginosa and L. monocytogenes. To characterize AMP activity within the B2M sequence, peptide fragments of the molecule were tested for antimicrobial activity. Activity could be localized to the C-terminal part of B2M. Investigating pH dependency of the antimicrobial activity of B2M demonstrated an increased activity at pH values of 5.5 and below, a hallmark of infection and inflammation. Sytox green uptake into bacterial cells following the exposure to B2M was determined and revealed a pH-dependent loss of bacterial membrane integrity. TEM analysis showed areas of disrupted bacterial membranes in L. monocytogenes incubated with B2M and high amounts of lysed bacterial cells. In conclusion, B2M as part of a ubiquitous cell surface complex may represent a potent antimicrobial agent by interfering with bacterial membrane integrity.Armin HolchRichard BauerLia-Raluca OlariArmando A. RodriguezLudger StändkerNico PreisingMerve KaracanSebastian WiesePaul WaltherYasser B. Ruiz-BlancoElsa Sanchez-GarciaChristian SchumannJan MünchBarbara SpellerbergTaylor & Francis Grouparticleß2-microglobulinantimicrobial peptidesinnate immunityphamyloidInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 1402-1414 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	ß2-microglobulin antimicrobial peptides innate immunity ph amyloid Infectious and parasitic diseases RC109-216
spellingShingle	ß2-microglobulin antimicrobial peptides innate immunity ph amyloid Infectious and parasitic diseases RC109-216 Armin Holch Richard Bauer Lia-Raluca Olari Armando A. Rodriguez Ludger Ständker Nico Preising Merve Karacan Sebastian Wiese Paul Walther Yasser B. Ruiz-Blanco Elsa Sanchez-Garcia Christian Schumann Jan Münch Barbara Spellerberg Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity
description	The respiratory tract is a major entry site for microbial pathogens. To combat bacterial infections, the immune system has various defense mechanisms at its disposal, including antimicrobial peptides (AMPs). To search for novel AMPs from the respiratory tract, a peptide library from human broncho-alveolar-lavage (BAL) fluid was screened for antimicrobial activity by radial diffusion assays allowing the efficient detection of antibacterial activity within a small sample size. After repeated testing-cycles and subsequent purification, we identified ß-2-microglobulin (B2M) in antibacterially active fractions. B2M belongs to the MHC-1 receptor complex present at the surface of nucleated cells. It is known to inhibit the growth of Listeria monocytogenes and Escherichia coli and to facilitate phagocytosis of Staphylococcus aureus. Using commercially available B2M we confirmed a dose-dependent inhibition of Pseudomonas aeruginosa and L. monocytogenes. To characterize AMP activity within the B2M sequence, peptide fragments of the molecule were tested for antimicrobial activity. Activity could be localized to the C-terminal part of B2M. Investigating pH dependency of the antimicrobial activity of B2M demonstrated an increased activity at pH values of 5.5 and below, a hallmark of infection and inflammation. Sytox green uptake into bacterial cells following the exposure to B2M was determined and revealed a pH-dependent loss of bacterial membrane integrity. TEM analysis showed areas of disrupted bacterial membranes in L. monocytogenes incubated with B2M and high amounts of lysed bacterial cells. In conclusion, B2M as part of a ubiquitous cell surface complex may represent a potent antimicrobial agent by interfering with bacterial membrane integrity.
format	article
author	Armin Holch Richard Bauer Lia-Raluca Olari Armando A. Rodriguez Ludger Ständker Nico Preising Merve Karacan Sebastian Wiese Paul Walther Yasser B. Ruiz-Blanco Elsa Sanchez-Garcia Christian Schumann Jan Münch Barbara Spellerberg
author_facet	Armin Holch Richard Bauer Lia-Raluca Olari Armando A. Rodriguez Ludger Ständker Nico Preising Merve Karacan Sebastian Wiese Paul Walther Yasser B. Ruiz-Blanco Elsa Sanchez-Garcia Christian Schumann Jan Münch Barbara Spellerberg
author_sort	Armin Holch
title	Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity
title_short	Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity
title_full	Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity
title_fullStr	Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity
title_full_unstemmed	Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity
title_sort	respiratory ß-2-microglobulin exerts ph dependent antimicrobial activity
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/f10bbf2e1585497dbe0729aeccdbea55
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Respiratory ß-2-Microglobulin exerts pH dependent antimicrobial activity

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