Engineered Bacillus subtilis WB600/ZD prevents Salmonella Infantis-induced intestinal inflammation and alters the colon microbiota in a mouse model

Abstract Antimicrobial peptides (AMPs) are instrumental in maintaining intestinal homeostasis and have emerged as potential therapeutic candidates for ameliorating intestinal bacterial infections. However, the intrinsic instability associated with the in vivo delivery of AMPs constitutes a substanti...

Full description

Saved in:
Bibliographic Details
Main Authors: Wei Li, Xue Wang, Keyuan Chen, Yaohong Zhu, Guiyan Yang, Yipeng Jin, Jiufeng Wang
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Veterinary Research
Subjects:
Online Access:https://doi.org/10.1186/s13567-024-01438-z
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1823861710204698624
author Wei Li
Xue Wang
Keyuan Chen
Yaohong Zhu
Guiyan Yang
Yipeng Jin
Jiufeng Wang
author_facet Wei Li
Xue Wang
Keyuan Chen
Yaohong Zhu
Guiyan Yang
Yipeng Jin
Jiufeng Wang
author_sort Wei Li
collection DOAJ
description Abstract Antimicrobial peptides (AMPs) are instrumental in maintaining intestinal homeostasis and have emerged as potential therapeutic candidates for ameliorating intestinal bacterial infections. However, the intrinsic instability associated with the in vivo delivery of AMPs constitutes a substantial impediment to their therapeutic efficacy in treating infections. In this study, we genetically modified Bacillus subtilis (B. subtilis) WB600 to express Zophobas atratus defensin (ZD), an antimicrobial peptide with broad-spectrum activity isolated from Zophobas atratus, for oral administration. This engineered strain effectively protects against Salmonella Infantis (S. Infantis) infection in mice. Pretreatment with WB600/ZD prevented NF-κB pathway activation induced by S. Infantis infection and increased expression of antioxidant and tight junction proteins, thus alleviating the severity of intestinal inflammation in both the jejunum and ileum (P < 0.01). Moreover, WB600/ZD pretreatment facilitated the growth of beneficial bacteria such as Lachnospiraceae, Butyricicoccus, Eubacterium_xylanophilum, and Clostridia_UCG-014 while decreasing the abundance of pathogenic bacteria such as Escherichia-Shigella and Salmonella (P < 0.05). In conclusion, this study underscores the protective effects of WB600/ZD on S. Infantis-induced intestinal inflammation, suggesting that oral delivery of B. subtilis WB600/ZD may be a promising prophylactic strategy for combating bacterial infections in the intestine.
format Article
id doaj-art-3322425a9ef64ebc88583bfe4bf01d08
institution Kabale University
issn 1297-9716
language English
publishDate 2025-02-01
publisher BMC
record_format Article
series Veterinary Research
spelling doaj-art-3322425a9ef64ebc88583bfe4bf01d082025-02-09T12:50:03ZengBMCVeterinary Research1297-97162025-02-0156111610.1186/s13567-024-01438-zEngineered Bacillus subtilis WB600/ZD prevents Salmonella Infantis-induced intestinal inflammation and alters the colon microbiota in a mouse modelWei Li0Xue Wang1Keyuan Chen2Yaohong Zhu3Guiyan Yang4Yipeng Jin5Jiufeng Wang6College of Veterinary Medicine, China Agricultural UniversityCollege of Veterinary Medicine, Inner Mongolia Agricultural UniversityCollege of Veterinary Medicine, China Agricultural UniversityCollege of Veterinary Medicine, China Agricultural UniversityCollege of Veterinary Medicine, China Agricultural UniversityCollege of Veterinary Medicine, China Agricultural UniversityCollege of Veterinary Medicine, China Agricultural UniversityAbstract Antimicrobial peptides (AMPs) are instrumental in maintaining intestinal homeostasis and have emerged as potential therapeutic candidates for ameliorating intestinal bacterial infections. However, the intrinsic instability associated with the in vivo delivery of AMPs constitutes a substantial impediment to their therapeutic efficacy in treating infections. In this study, we genetically modified Bacillus subtilis (B. subtilis) WB600 to express Zophobas atratus defensin (ZD), an antimicrobial peptide with broad-spectrum activity isolated from Zophobas atratus, for oral administration. This engineered strain effectively protects against Salmonella Infantis (S. Infantis) infection in mice. Pretreatment with WB600/ZD prevented NF-κB pathway activation induced by S. Infantis infection and increased expression of antioxidant and tight junction proteins, thus alleviating the severity of intestinal inflammation in both the jejunum and ileum (P < 0.01). Moreover, WB600/ZD pretreatment facilitated the growth of beneficial bacteria such as Lachnospiraceae, Butyricicoccus, Eubacterium_xylanophilum, and Clostridia_UCG-014 while decreasing the abundance of pathogenic bacteria such as Escherichia-Shigella and Salmonella (P < 0.05). In conclusion, this study underscores the protective effects of WB600/ZD on S. Infantis-induced intestinal inflammation, suggesting that oral delivery of B. subtilis WB600/ZD may be a promising prophylactic strategy for combating bacterial infections in the intestine.https://doi.org/10.1186/s13567-024-01438-zZophobas atratus defensinengineered bacteriaB. subtilis WB600/ZDS. Infantis infectionsmall intestinal inflammation
spellingShingle Wei Li
Xue Wang
Keyuan Chen
Yaohong Zhu
Guiyan Yang
Yipeng Jin
Jiufeng Wang
Engineered Bacillus subtilis WB600/ZD prevents Salmonella Infantis-induced intestinal inflammation and alters the colon microbiota in a mouse model
Veterinary Research
Zophobas atratus defensin
engineered bacteria
B. subtilis WB600/ZD
S. Infantis infection
small intestinal inflammation
title Engineered Bacillus subtilis WB600/ZD prevents Salmonella Infantis-induced intestinal inflammation and alters the colon microbiota in a mouse model
title_full Engineered Bacillus subtilis WB600/ZD prevents Salmonella Infantis-induced intestinal inflammation and alters the colon microbiota in a mouse model
title_fullStr Engineered Bacillus subtilis WB600/ZD prevents Salmonella Infantis-induced intestinal inflammation and alters the colon microbiota in a mouse model
title_full_unstemmed Engineered Bacillus subtilis WB600/ZD prevents Salmonella Infantis-induced intestinal inflammation and alters the colon microbiota in a mouse model
title_short Engineered Bacillus subtilis WB600/ZD prevents Salmonella Infantis-induced intestinal inflammation and alters the colon microbiota in a mouse model
title_sort engineered bacillus subtilis wb600 zd prevents salmonella infantis induced intestinal inflammation and alters the colon microbiota in a mouse model
topic Zophobas atratus defensin
engineered bacteria
B. subtilis WB600/ZD
S. Infantis infection
small intestinal inflammation
url https://doi.org/10.1186/s13567-024-01438-z
work_keys_str_mv AT weili engineeredbacillussubtiliswb600zdpreventssalmonellainfantisinducedintestinalinflammationandaltersthecolonmicrobiotainamousemodel
AT xuewang engineeredbacillussubtiliswb600zdpreventssalmonellainfantisinducedintestinalinflammationandaltersthecolonmicrobiotainamousemodel
AT keyuanchen engineeredbacillussubtiliswb600zdpreventssalmonellainfantisinducedintestinalinflammationandaltersthecolonmicrobiotainamousemodel
AT yaohongzhu engineeredbacillussubtiliswb600zdpreventssalmonellainfantisinducedintestinalinflammationandaltersthecolonmicrobiotainamousemodel
AT guiyanyang engineeredbacillussubtiliswb600zdpreventssalmonellainfantisinducedintestinalinflammationandaltersthecolonmicrobiotainamousemodel
AT yipengjin engineeredbacillussubtiliswb600zdpreventssalmonellainfantisinducedintestinalinflammationandaltersthecolonmicrobiotainamousemodel
AT jiufengwang engineeredbacillussubtiliswb600zdpreventssalmonellainfantisinducedintestinalinflammationandaltersthecolonmicrobiotainamousemodel