Metformin strengthens uroepithelial immunity against E. coli infection

Abstract Urinary tract infection frequently caused by E. coli is one of the most common bacterial infections. Increasing antibiotic resistance jeopardizes successful treatment and alternative treatment strategies are therefore mandatory. Metformin, an oral antidiabetic drug, has been shown to activa...

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Autores principales:	Rakesh Kumar Majhi, Soumitra Mohanty, Witchuda Kamolvit, John Kerr White, Andrea Scheffschick, Hanna Brauner, Annelie Brauner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3459b6827d2349b68c7af209abb0f3b0
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spelling	oai:doaj.org-article:3459b6827d2349b68c7af209abb0f3b02021-12-02T17:37:40ZMetformin strengthens uroepithelial immunity against E. coli infection10.1038/s41598-021-98223-12045-2322https://doaj.org/article/3459b6827d2349b68c7af209abb0f3b02021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98223-1https://doaj.org/toc/2045-2322Abstract Urinary tract infection frequently caused by E. coli is one of the most common bacterial infections. Increasing antibiotic resistance jeopardizes successful treatment and alternative treatment strategies are therefore mandatory. Metformin, an oral antidiabetic drug, has been shown to activate macrophages in the protection against certain infecting microorganisms. Since epithelial cells often form the first line of defense, we here investigated the effect on uroepithelial cells during E. coli infection. Metformin upregulated the human antimicrobial peptides cathelicidin LL-37 and RNase7 via modulation of the TRPA1 channel and AMPK pathway. Interestingly, metformin stimulation enriched both LL-37 and TRPA1 in lysosomes. In addition, metformin specifically increased nitric oxide and mitochondrial, but not cytosolic ROS. Moreover, metformin also triggered mRNA expression of the proinflammatory cytokines IL1B, CXCL8 and growth factor GDF15 in human uroepithelial cells. The GDF15 peptide stimulated macrophages increased LL-37 expression, with increased bacterial killing. In conclusion, metformin stimulation strengthened the innate immunity of uroepithelial cells inducing enhanced extracellular and intracellular bacterial killing suggesting a favorable role of metformin in the host defense.Rakesh Kumar MajhiSoumitra MohantyWitchuda KamolvitJohn Kerr WhiteAndrea ScheffschickHanna BraunerAnnelie BraunerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rakesh Kumar Majhi Soumitra Mohanty Witchuda Kamolvit John Kerr White Andrea Scheffschick Hanna Brauner Annelie Brauner Metformin strengthens uroepithelial immunity against E. coli infection
description	Abstract Urinary tract infection frequently caused by E. coli is one of the most common bacterial infections. Increasing antibiotic resistance jeopardizes successful treatment and alternative treatment strategies are therefore mandatory. Metformin, an oral antidiabetic drug, has been shown to activate macrophages in the protection against certain infecting microorganisms. Since epithelial cells often form the first line of defense, we here investigated the effect on uroepithelial cells during E. coli infection. Metformin upregulated the human antimicrobial peptides cathelicidin LL-37 and RNase7 via modulation of the TRPA1 channel and AMPK pathway. Interestingly, metformin stimulation enriched both LL-37 and TRPA1 in lysosomes. In addition, metformin specifically increased nitric oxide and mitochondrial, but not cytosolic ROS. Moreover, metformin also triggered mRNA expression of the proinflammatory cytokines IL1B, CXCL8 and growth factor GDF15 in human uroepithelial cells. The GDF15 peptide stimulated macrophages increased LL-37 expression, with increased bacterial killing. In conclusion, metformin stimulation strengthened the innate immunity of uroepithelial cells inducing enhanced extracellular and intracellular bacterial killing suggesting a favorable role of metformin in the host defense.
format	article
author	Rakesh Kumar Majhi Soumitra Mohanty Witchuda Kamolvit John Kerr White Andrea Scheffschick Hanna Brauner Annelie Brauner
author_facet	Rakesh Kumar Majhi Soumitra Mohanty Witchuda Kamolvit John Kerr White Andrea Scheffschick Hanna Brauner Annelie Brauner
author_sort	Rakesh Kumar Majhi
title	Metformin strengthens uroepithelial immunity against E. coli infection
title_short	Metformin strengthens uroepithelial immunity against E. coli infection
title_full	Metformin strengthens uroepithelial immunity against E. coli infection
title_fullStr	Metformin strengthens uroepithelial immunity against E. coli infection
title_full_unstemmed	Metformin strengthens uroepithelial immunity against E. coli infection
title_sort	metformin strengthens uroepithelial immunity against e. coli infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3459b6827d2349b68c7af209abb0f3b0
work_keys_str_mv	AT rakeshkumarmajhi metforminstrengthensuroepithelialimmunityagainstecoliinfection AT soumitramohanty metforminstrengthensuroepithelialimmunityagainstecoliinfection AT witchudakamolvit metforminstrengthensuroepithelialimmunityagainstecoliinfection AT johnkerrwhite metforminstrengthensuroepithelialimmunityagainstecoliinfection AT andreascheffschick metforminstrengthensuroepithelialimmunityagainstecoliinfection AT hannabrauner metforminstrengthensuroepithelialimmunityagainstecoliinfection AT anneliebrauner metforminstrengthensuroepithelialimmunityagainstecoliinfection
_version_	1718379875313647616

Metformin strengthens uroepithelial immunity against E. coli infection

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