The molybdate transport protein ModA regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of Klebsiella pneumoniae in the inflamed gut

The mammalian intestine is a major site of colonization and a starting point of severe infections by Klebsiella pneumoniae. Inflammatory bowel disease (IBD) is an inflammatory disorder of the gut, and host-derived nitrate in IBD confers a luminal growth advantage upon Escherichia coli and Salmonella...

Full description

Saved in:
Bibliographic Details
Main Authors: Jichen Xie, Hui Wang, Renhui Ma, Jinming Fan, Qiuhang Quan, Zhiqiang Zhang, Moran Li, Bei Li
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Virulence
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/21505594.2025.2474185
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850109285252464640
author Jichen Xie
Hui Wang
Renhui Ma
Jinming Fan
Qiuhang Quan
Zhiqiang Zhang
Moran Li
Bei Li
author_facet Jichen Xie
Hui Wang
Renhui Ma
Jinming Fan
Qiuhang Quan
Zhiqiang Zhang
Moran Li
Bei Li
author_sort Jichen Xie
collection DOAJ
description The mammalian intestine is a major site of colonization and a starting point of severe infections by Klebsiella pneumoniae. Inflammatory bowel disease (IBD) is an inflammatory disorder of the gut, and host-derived nitrate in IBD confers a luminal growth advantage upon Escherichia coli and Salmonella typhimurium through nitrate respiration in the inflamed gut. However, the impact of nitrate on the growth and pathogenicity of K. pneumoniae in this microenvironment is poorly understood. In this study, we used oral administration of dextran sodium sulphate to induce IBD in mouse models. We then analysed the colonization levels of K. pneumoniae wild-type (WT), the nitrate reductase gene mutant strains (ΔnarG, ΔnarZ and ΔnarGΔnarZ), and the molybdate uptake gene mutant strain (ΔmodA) in the inflamed intestinal tract. Results showed that the growth, intestinal colonization, and extraintestinal dissemination of K. pneumoniae were increased in the intestines of dextran sulphate sodium (DSS)-treated mice. Nitrate in the inflamed bowel conferred a growth advantage to K. pneumoniae through nitrate respiration. The molybdate transport protein ModA regulated nitrate reductase activity to increase the growth, intestinal colonization, and extraintestinal dissemination of K. pneumoniae. Tungstate will be a promising antibacterial agent to tackle K. pneumoniae infections in IBD patients.
format Article
id doaj-art-439fb1db2ea24d76b8f455e071ce9b13
institution OA Journals
issn 2150-5594
2150-5608
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
record_format Article
series Virulence
spelling doaj-art-439fb1db2ea24d76b8f455e071ce9b132025-08-20T02:38:06ZengTaylor & Francis GroupVirulence2150-55942150-56082025-12-0116110.1080/21505594.2025.2474185The molybdate transport protein ModA regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of Klebsiella pneumoniae in the inflamed gutJichen Xie0Hui Wang1Renhui Ma2Jinming Fan3Qiuhang Quan4Zhiqiang Zhang5Moran Li6Bei Li7School of Basic Medical Science, Hubei University of Medicine, Shiyan, ChinaSchool of Basic Medical Science, Hubei University of Medicine, Shiyan, ChinaSchool of Basic Medical Science, Hubei University of Medicine, Shiyan, ChinaSchool of Basic Medical Science, Hubei University of Medicine, Shiyan, ChinaSchool of Basic Medical Science, Hubei University of Medicine, Shiyan, ChinaSchool of Basic Medical Science, Hubei University of Medicine, Shiyan, ChinaSchool of Basic Medical Science, Hubei University of Medicine, Shiyan, ChinaSchool of Basic Medical Science, Hubei University of Medicine, Shiyan, ChinaThe mammalian intestine is a major site of colonization and a starting point of severe infections by Klebsiella pneumoniae. Inflammatory bowel disease (IBD) is an inflammatory disorder of the gut, and host-derived nitrate in IBD confers a luminal growth advantage upon Escherichia coli and Salmonella typhimurium through nitrate respiration in the inflamed gut. However, the impact of nitrate on the growth and pathogenicity of K. pneumoniae in this microenvironment is poorly understood. In this study, we used oral administration of dextran sodium sulphate to induce IBD in mouse models. We then analysed the colonization levels of K. pneumoniae wild-type (WT), the nitrate reductase gene mutant strains (ΔnarG, ΔnarZ and ΔnarGΔnarZ), and the molybdate uptake gene mutant strain (ΔmodA) in the inflamed intestinal tract. Results showed that the growth, intestinal colonization, and extraintestinal dissemination of K. pneumoniae were increased in the intestines of dextran sulphate sodium (DSS)-treated mice. Nitrate in the inflamed bowel conferred a growth advantage to K. pneumoniae through nitrate respiration. The molybdate transport protein ModA regulated nitrate reductase activity to increase the growth, intestinal colonization, and extraintestinal dissemination of K. pneumoniae. Tungstate will be a promising antibacterial agent to tackle K. pneumoniae infections in IBD patients.https://www.tandfonline.com/doi/10.1080/21505594.2025.2474185IBDKlebsiella pneumoniaeModAnitrate reductaseintestinal colonization
spellingShingle Jichen Xie
Hui Wang
Renhui Ma
Jinming Fan
Qiuhang Quan
Zhiqiang Zhang
Moran Li
Bei Li
The molybdate transport protein ModA regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of Klebsiella pneumoniae in the inflamed gut
Virulence
IBD
Klebsiella pneumoniae
ModA
nitrate reductase
intestinal colonization
title The molybdate transport protein ModA regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of Klebsiella pneumoniae in the inflamed gut
title_full The molybdate transport protein ModA regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of Klebsiella pneumoniae in the inflamed gut
title_fullStr The molybdate transport protein ModA regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of Klebsiella pneumoniae in the inflamed gut
title_full_unstemmed The molybdate transport protein ModA regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of Klebsiella pneumoniae in the inflamed gut
title_short The molybdate transport protein ModA regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of Klebsiella pneumoniae in the inflamed gut
title_sort molybdate transport protein moda regulates nitrate reductase activity to increase the intestinal colonization and extraintestinal dissemination of klebsiella pneumoniae in the inflamed gut
topic IBD
Klebsiella pneumoniae
ModA
nitrate reductase
intestinal colonization
url https://www.tandfonline.com/doi/10.1080/21505594.2025.2474185
work_keys_str_mv AT jichenxie themolybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT huiwang themolybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT renhuima themolybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT jinmingfan themolybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT qiuhangquan themolybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT zhiqiangzhang themolybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT moranli themolybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT beili themolybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT jichenxie molybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT huiwang molybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT renhuima molybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT jinmingfan molybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT qiuhangquan molybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT zhiqiangzhang molybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT moranli molybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut
AT beili molybdatetransportproteinmodaregulatesnitratereductaseactivitytoincreasetheintestinalcolonizationandextraintestinaldisseminationofklebsiellapneumoniaeintheinflamedgut