Lasso Peptide Microcin J25 Effectively Enhances Gut Barrier Function and Modulates Inflammatory Response in an Enterotoxigenic <i>Escherichia coli</i>-Challenged Mouse Model
Bacterial resistance leads to severe public health and safety issues worldwide. Alternatives to antibiotics are currently needed. A promising lasso peptide, microcin J25 (MccJ25), is considered to be the best potential substitute for antibiotics to treat pathogen infection, including enterotoxigenic...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6500 |
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| author | Xiuliang Ding Haitao Yu Shiyan Qiao |
| author_facet | Xiuliang Ding Haitao Yu Shiyan Qiao |
| author_sort | Xiuliang Ding |
| collection | DOAJ |
| description | Bacterial resistance leads to severe public health and safety issues worldwide. Alternatives to antibiotics are currently needed. A promising lasso peptide, microcin J25 (MccJ25), is considered to be the best potential substitute for antibiotics to treat pathogen infection, including enterotoxigenic <i>Escherichia coli</i> (ETEC). This study evaluated the efficacy of MccJ25 in the prevention of ETEC infection. Forty-five female BALB/c mice of clean grade (aged seven weeks, approximately 16.15 g) were randomly divided into three experimental groups as follows: (i) control group (uninfected); (ii) ETEC infection group; (iii) MccJ25 + ETEC group. Fifteen mice per group in five cages, three mice/cage. MccJ25 conferred effective protection against ETEC-induced body weight loss, decrease in rectal temperature and increase in diarrhea scores in mice. Moreover, in ETEC-challenged mice model, MccJ25 significantly improved intestinal morphology, decreased intestinal histopathological scores and attenuated intestinal inflammation by decreasing proinflammatory cytokines and intestinal permeability, including reducing serum diamine oxidase and D-lactate levels. MccJ25 enhanced epithelial barrier function by increasing occludin expression in the colon and claudin-1 expression in the jejunum, ultimately improving intestinal health of host. MccJ25 was further found to alleviate gut inflammatory responses by decreasing inflammatory cytokine production and expression via the activation of the mitogen-activated protein kinase and nuclear factor κB signaling pathways. Taken together, the results indicated that MccJ25 protects against ETEC-induced intestinal injury and intestinal inflammatory responses, suggesting the potential application of MccJ25 as an excellent antimicrobial or anti-inflammation agent against pathogen infections. |
| first_indexed | 2024-03-10T16:32:27Z |
| format | Article |
| id | doaj.art-096e56250db54d578873eea217bceaed |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:32:27Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-096e56250db54d578873eea217bceaed2023-11-20T12:42:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118650010.3390/ijms21186500Lasso Peptide Microcin J25 Effectively Enhances Gut Barrier Function and Modulates Inflammatory Response in an Enterotoxigenic <i>Escherichia coli</i>-Challenged Mouse ModelXiuliang Ding0Haitao Yu1Shiyan Qiao2State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Center, China Agricultural University, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Center, China Agricultural University, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Center, China Agricultural University, Beijing 100193, ChinaBacterial resistance leads to severe public health and safety issues worldwide. Alternatives to antibiotics are currently needed. A promising lasso peptide, microcin J25 (MccJ25), is considered to be the best potential substitute for antibiotics to treat pathogen infection, including enterotoxigenic <i>Escherichia coli</i> (ETEC). This study evaluated the efficacy of MccJ25 in the prevention of ETEC infection. Forty-five female BALB/c mice of clean grade (aged seven weeks, approximately 16.15 g) were randomly divided into three experimental groups as follows: (i) control group (uninfected); (ii) ETEC infection group; (iii) MccJ25 + ETEC group. Fifteen mice per group in five cages, three mice/cage. MccJ25 conferred effective protection against ETEC-induced body weight loss, decrease in rectal temperature and increase in diarrhea scores in mice. Moreover, in ETEC-challenged mice model, MccJ25 significantly improved intestinal morphology, decreased intestinal histopathological scores and attenuated intestinal inflammation by decreasing proinflammatory cytokines and intestinal permeability, including reducing serum diamine oxidase and D-lactate levels. MccJ25 enhanced epithelial barrier function by increasing occludin expression in the colon and claudin-1 expression in the jejunum, ultimately improving intestinal health of host. MccJ25 was further found to alleviate gut inflammatory responses by decreasing inflammatory cytokine production and expression via the activation of the mitogen-activated protein kinase and nuclear factor κB signaling pathways. Taken together, the results indicated that MccJ25 protects against ETEC-induced intestinal injury and intestinal inflammatory responses, suggesting the potential application of MccJ25 as an excellent antimicrobial or anti-inflammation agent against pathogen infections.https://www.mdpi.com/1422-0067/21/18/6500enterotoxigenic <i>Escherichia coli</i>microcin J25intestinal epithelial barrierintestinal inflammationmicepathogen |
| spellingShingle | Xiuliang Ding Haitao Yu Shiyan Qiao Lasso Peptide Microcin J25 Effectively Enhances Gut Barrier Function and Modulates Inflammatory Response in an Enterotoxigenic <i>Escherichia coli</i>-Challenged Mouse Model International Journal of Molecular Sciences enterotoxigenic <i>Escherichia coli</i> microcin J25 intestinal epithelial barrier intestinal inflammation mice pathogen |
| title | Lasso Peptide Microcin J25 Effectively Enhances Gut Barrier Function and Modulates Inflammatory Response in an Enterotoxigenic <i>Escherichia coli</i>-Challenged Mouse Model |
| title_full | Lasso Peptide Microcin J25 Effectively Enhances Gut Barrier Function and Modulates Inflammatory Response in an Enterotoxigenic <i>Escherichia coli</i>-Challenged Mouse Model |
| title_fullStr | Lasso Peptide Microcin J25 Effectively Enhances Gut Barrier Function and Modulates Inflammatory Response in an Enterotoxigenic <i>Escherichia coli</i>-Challenged Mouse Model |
| title_full_unstemmed | Lasso Peptide Microcin J25 Effectively Enhances Gut Barrier Function and Modulates Inflammatory Response in an Enterotoxigenic <i>Escherichia coli</i>-Challenged Mouse Model |
| title_short | Lasso Peptide Microcin J25 Effectively Enhances Gut Barrier Function and Modulates Inflammatory Response in an Enterotoxigenic <i>Escherichia coli</i>-Challenged Mouse Model |
| title_sort | lasso peptide microcin j25 effectively enhances gut barrier function and modulates inflammatory response in an enterotoxigenic i escherichia coli i challenged mouse model |
| topic | enterotoxigenic <i>Escherichia coli</i> microcin J25 intestinal epithelial barrier intestinal inflammation mice pathogen |
| url | https://www.mdpi.com/1422-0067/21/18/6500 |
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