Gut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing <i>Escherichia coli</i>

Shiga toxin-producing <i>Escherichia coli</i> (STEC) infects humans by colonizing the large intestine, and causes kidney damage by secreting Shiga toxins (Stxs). The increased secretion of Shiga toxin 2 (Stx2) by some antibiotics, such as ciprofloxacin (CIP), increases the risk of hemoly...

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Autores principales:	Yugyeong Lee, Min-Hyeok Kim, David Rodrigues Alves, Sejoong Kim, Luke P. Lee, Jong Hwan Sung, Sungsu Park
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hemolytic–uremic syndrome (HUS) multi-organ-on-a-chip <i>Escherichia coli</i> infection antibiotics Shiga toxin Medicine R
Acceso en línea:	https://doaj.org/article/47b4bf36412645b394b055f06cc19efd
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spelling	oai:doaj.org-article:47b4bf36412645b394b055f06cc19efd2021-11-25T19:08:44ZGut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing <i>Escherichia coli</i>10.3390/toxins131107752072-6651https://doaj.org/article/47b4bf36412645b394b055f06cc19efd2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6651/13/11/775https://doaj.org/toc/2072-6651Shiga toxin-producing <i>Escherichia coli</i> (STEC) infects humans by colonizing the large intestine, and causes kidney damage by secreting Shiga toxins (Stxs). The increased secretion of Shiga toxin 2 (Stx2) by some antibiotics, such as ciprofloxacin (CIP), increases the risk of hemolytic–uremic syndrome (HUS), which can be life-threatening. However, previous studies evaluating this relationship have been conflicting, owing to the low frequency of EHEC infection, very small number of patients, and lack of an appropriate animal model. In this study, we developed gut–kidney axis (GKA) on chip for co-culturing gut (Caco-2) and kidney (HKC-8) cells, and observed both STEC O157:H7 (O157) infection and Stx intoxication in the gut and kidney cells on the chip, respectively. Without any antibiotic treatment, O157 killed both gut and kidney cells in GKA on the chip. CIP treatment reduced O157 infection in the gut cells, but increased Stx2-induced damage in the kidney cells, whereas the gentamycin treatment reduced both O157 infection in the gut cells and Stx2-induced damage in the kidney cells. This is the first report to recapitulate a clinically relevant situation, i.e., that CIP treatment causes more damage than gentamicin treatment. These results suggest that GKA on chip is very useful for simultaneous observation of O157 infections and Stx2 poisoning in gut and kidney cells, making it suitable for studying the effects of antibiotics on the risk of HUS.Yugyeong LeeMin-Hyeok KimDavid Rodrigues AlvesSejoong KimLuke P. LeeJong Hwan SungSungsu ParkMDPI AGarticlehemolytic–uremic syndrome (HUS)multi-organ-on-a-chip<i>Escherichia coli</i> infectionantibioticsShiga toxinMedicineRENToxins, Vol 13, Iss 775, p 775 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hemolytic–uremic syndrome (HUS) multi-organ-on-a-chip <i>Escherichia coli</i> infection antibiotics Shiga toxin Medicine R
spellingShingle	hemolytic–uremic syndrome (HUS) multi-organ-on-a-chip <i>Escherichia coli</i> infection antibiotics Shiga toxin Medicine R Yugyeong Lee Min-Hyeok Kim David Rodrigues Alves Sejoong Kim Luke P. Lee Jong Hwan Sung Sungsu Park Gut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing <i>Escherichia coli</i>
description	Shiga toxin-producing <i>Escherichia coli</i> (STEC) infects humans by colonizing the large intestine, and causes kidney damage by secreting Shiga toxins (Stxs). The increased secretion of Shiga toxin 2 (Stx2) by some antibiotics, such as ciprofloxacin (CIP), increases the risk of hemolytic–uremic syndrome (HUS), which can be life-threatening. However, previous studies evaluating this relationship have been conflicting, owing to the low frequency of EHEC infection, very small number of patients, and lack of an appropriate animal model. In this study, we developed gut–kidney axis (GKA) on chip for co-culturing gut (Caco-2) and kidney (HKC-8) cells, and observed both STEC O157:H7 (O157) infection and Stx intoxication in the gut and kidney cells on the chip, respectively. Without any antibiotic treatment, O157 killed both gut and kidney cells in GKA on the chip. CIP treatment reduced O157 infection in the gut cells, but increased Stx2-induced damage in the kidney cells, whereas the gentamycin treatment reduced both O157 infection in the gut cells and Stx2-induced damage in the kidney cells. This is the first report to recapitulate a clinically relevant situation, i.e., that CIP treatment causes more damage than gentamicin treatment. These results suggest that GKA on chip is very useful for simultaneous observation of O157 infections and Stx2 poisoning in gut and kidney cells, making it suitable for studying the effects of antibiotics on the risk of HUS.
format	article
author	Yugyeong Lee Min-Hyeok Kim David Rodrigues Alves Sejoong Kim Luke P. Lee Jong Hwan Sung Sungsu Park
author_facet	Yugyeong Lee Min-Hyeok Kim David Rodrigues Alves Sejoong Kim Luke P. Lee Jong Hwan Sung Sungsu Park
author_sort	Yugyeong Lee
title	Gut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing <i>Escherichia coli</i>
title_short	Gut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing <i>Escherichia coli</i>
title_full	Gut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing <i>Escherichia coli</i>
title_fullStr	Gut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing <i>Escherichia coli</i>
title_full_unstemmed	Gut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing <i>Escherichia coli</i>
title_sort	gut–kidney axis on chip for studying effects of antibiotics on risk of hemolytic uremic syndrome by shiga toxin-producing <i>escherichia coli</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/47b4bf36412645b394b055f06cc19efd
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Gut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing <i>Escherichia coli</i>

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