<i>Bis</i>(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria

The compounds referred to as <i>bis</i>(tryptophan)s (BTs) have shown activity as antimicrobials. The hypothesis that the activity of these novel amphiphiles results from insertion in bilayer membranes and transport of cations is supported by planar bilayer voltage-clamp studies reported...

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Autores principales:	Mohit Patel, Saeedeh Negin, Joseph Meisel, Shanheng Yin, Michael Gokel, Hannah Gill, George Gokel
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	adjuvant amino acids amphiphile antimicrobial bacteria efflux pump Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/8f649761008d4153a5a2cd09c744493e
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spelling	oai:doaj.org-article:8f649761008d4153a5a2cd09c744493e2021-11-25T16:24:35Z<i>Bis</i>(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria10.3390/antibiotics101113912079-6382https://doaj.org/article/8f649761008d4153a5a2cd09c744493e2021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1391https://doaj.org/toc/2079-6382The compounds referred to as <i>bis</i>(tryptophan)s (BTs) have shown activity as antimicrobials. The hypothesis that the activity of these novel amphiphiles results from insertion in bilayer membranes and transport of cations is supported by planar bilayer voltage-clamp studies reported herein. In addition, fluorescence studies of propidium iodide penetration of vital bacteria confirmed enhanced permeability. It was also found that BTs having either meta-phenylene or n-dodecylene linkers function as effective adjuvants to enhance the properties of FDA-approved antimicrobials against organisms such as <i>S. aureus</i>. In one example, a BT-mediated synergistic effect enhanced the potency of norfloxacin against <i>S. aureus</i> by 128-fold. In order to determine if related compounds in which tryptophan was replaced by other common amino acids (H<sub>2</sub>N-Aaa-linker-Aaa-NH<sub>2</sub>) we active, a family of analogs have been prepared, characterized, and tested as controls for both antimicrobial activity and as adjuvants for other antimicrobials against both Gram-negative and Gram-positive bacteria. The most active of the compounds surveyed remain the bis(tryptophan) derivatives.Mohit PatelSaeedeh NeginJoseph MeiselShanheng YinMichael GokelHannah GillGeorge GokelMDPI AGarticleadjuvantamino acidsamphiphileantimicrobialbacteriaefflux pumpTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1391, p 1391 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adjuvant amino acids amphiphile antimicrobial bacteria efflux pump Therapeutics. Pharmacology RM1-950
spellingShingle	adjuvant amino acids amphiphile antimicrobial bacteria efflux pump Therapeutics. Pharmacology RM1-950 Mohit Patel Saeedeh Negin Joseph Meisel Shanheng Yin Michael Gokel Hannah Gill George Gokel <i>Bis</i>(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria
description	The compounds referred to as <i>bis</i>(tryptophan)s (BTs) have shown activity as antimicrobials. The hypothesis that the activity of these novel amphiphiles results from insertion in bilayer membranes and transport of cations is supported by planar bilayer voltage-clamp studies reported herein. In addition, fluorescence studies of propidium iodide penetration of vital bacteria confirmed enhanced permeability. It was also found that BTs having either meta-phenylene or n-dodecylene linkers function as effective adjuvants to enhance the properties of FDA-approved antimicrobials against organisms such as <i>S. aureus</i>. In one example, a BT-mediated synergistic effect enhanced the potency of norfloxacin against <i>S. aureus</i> by 128-fold. In order to determine if related compounds in which tryptophan was replaced by other common amino acids (H<sub>2</sub>N-Aaa-linker-Aaa-NH<sub>2</sub>) we active, a family of analogs have been prepared, characterized, and tested as controls for both antimicrobial activity and as adjuvants for other antimicrobials against both Gram-negative and Gram-positive bacteria. The most active of the compounds surveyed remain the bis(tryptophan) derivatives.
format	article
author	Mohit Patel Saeedeh Negin Joseph Meisel Shanheng Yin Michael Gokel Hannah Gill George Gokel
author_facet	Mohit Patel Saeedeh Negin Joseph Meisel Shanheng Yin Michael Gokel Hannah Gill George Gokel
author_sort	Mohit Patel
title	<i>Bis</i>(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria
title_short	<i>Bis</i>(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria
title_full	<i>Bis</i>(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria
title_fullStr	<i>Bis</i>(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria
title_full_unstemmed	<i>Bis</i>(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria
title_sort	<i>bis</i>(tryptophan) amphiphiles form ion conducting pores and enhance antimicrobial activity against resistant bacteria
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8f649761008d4153a5a2cd09c744493e
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<i>Bis</i>(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria

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