16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer
Abstract Background Diabetic foot ulcer (DFU) is one of the main chronic complications caused by diabetes, leading to amputation in severe cases. Bacterial infection affects the wound healing in DFU. Methods DFU patients who met the criteria were selected, and the clinical data were recorded in deta...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-024-09235-x |
| _version_ | 1827291692272713728 |
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| author | Hailong Zheng Han Na Jiangling Yao Sheng Su Feng Han Xiaoyan Li Xiaopan Chen |
| author_facet | Hailong Zheng Han Na Jiangling Yao Sheng Su Feng Han Xiaoyan Li Xiaopan Chen |
| author_sort | Hailong Zheng |
| collection | DOAJ |
| description | Abstract Background Diabetic foot ulcer (DFU) is one of the main chronic complications caused by diabetes, leading to amputation in severe cases. Bacterial infection affects the wound healing in DFU. Methods DFU patients who met the criteria were selected, and the clinical data were recorded in detail. The pus exudate from the patient’s foot wound and venous blood were collected for biochemical analysis. The distribution of bacterial flora in pus exudates of patients was analyzed by 16S rRNA sequencing, and the correlation between DFU and pathogenic variables, pyroptosis and immunity was analyzed by statistical analysis. Then, the effects of key bacteria on the inflammation, proliferation, apoptosis, and pyroptosis of polymorphonuclear leukocytes were investigated by ELISA, CCK-8, flow cytometry, RT-qPCR and western blot. Results Clinical data analysis showed that Wagner score was positively correlated with the level of inflammatory factors, and there was high CD3+, CD4+, and low CD8+ levels in DFU patients with high Wagner score. Through alpha, beta diversity analysis and species composition analysis, Corynebacterium accounted for a large proportion in DFU. Logistics regression model and Person correlation analysis demonstrated that mixed bacterial infections could aggravate foot ulcer, and the number of bacteria was closely related to inflammatory factors PCT, PRT, immune cells CD8+, and pyroptosis-related proteins GSDMD and NLRP3. Through in vitro experiments, Corynebacterium inhibited cell proliferation, promoted inflammation (TNF-α, PCT, CRP), apoptosis and pyroptosis (IL-1β, LDH, IL-18, GSDMD, NLRP3, and caspase-3). Conclusion Mixed bacterial infections exacerbate DFU progression with a high predominance of Corynebacterium, and Corynebacterium promotes inflammation, apoptosis and pyroptosis to inhibit DFU healing. |
| first_indexed | 2024-04-24T12:42:15Z |
| format | Article |
| id | doaj.art-1f787b2021d94e90b6dd0a724cb8d5a2 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-04-24T12:42:15Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-1f787b2021d94e90b6dd0a724cb8d5a22024-04-07T11:09:53ZengBMCBMC Infectious Diseases1471-23342024-04-0124111110.1186/s12879-024-09235-x16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcerHailong Zheng0Han Na1Jiangling Yao2Sheng Su3Feng Han4Xiaoyan Li5Xiaopan Chen6Department of Endocrinology, The First Affiliated Hospital of Hainan Medical University, Hainan ProvinceDepartment of Endocrinology, The First Affiliated Hospital of Hainan Medical University, Hainan ProvinceDepartment of Wound Repair, The First Affiliated Hospital of Hainan Medical University, Hainan ProvinceDepartment of Endocrinology, The First Affiliated Hospital of Hainan Medical University, Hainan ProvinceDepartment of Clinical Laboratory, The First Affiliated Hospital of Hainan Medical University, Hainan ProvinceDepartment of Endocrinology, The First Affiliated Hospital of Hainan Medical University, Hainan ProvinceDepartment of Endocrinology, The First Affiliated Hospital of Hainan Medical University, Hainan ProvinceAbstract Background Diabetic foot ulcer (DFU) is one of the main chronic complications caused by diabetes, leading to amputation in severe cases. Bacterial infection affects the wound healing in DFU. Methods DFU patients who met the criteria were selected, and the clinical data were recorded in detail. The pus exudate from the patient’s foot wound and venous blood were collected for biochemical analysis. The distribution of bacterial flora in pus exudates of patients was analyzed by 16S rRNA sequencing, and the correlation between DFU and pathogenic variables, pyroptosis and immunity was analyzed by statistical analysis. Then, the effects of key bacteria on the inflammation, proliferation, apoptosis, and pyroptosis of polymorphonuclear leukocytes were investigated by ELISA, CCK-8, flow cytometry, RT-qPCR and western blot. Results Clinical data analysis showed that Wagner score was positively correlated with the level of inflammatory factors, and there was high CD3+, CD4+, and low CD8+ levels in DFU patients with high Wagner score. Through alpha, beta diversity analysis and species composition analysis, Corynebacterium accounted for a large proportion in DFU. Logistics regression model and Person correlation analysis demonstrated that mixed bacterial infections could aggravate foot ulcer, and the number of bacteria was closely related to inflammatory factors PCT, PRT, immune cells CD8+, and pyroptosis-related proteins GSDMD and NLRP3. Through in vitro experiments, Corynebacterium inhibited cell proliferation, promoted inflammation (TNF-α, PCT, CRP), apoptosis and pyroptosis (IL-1β, LDH, IL-18, GSDMD, NLRP3, and caspase-3). Conclusion Mixed bacterial infections exacerbate DFU progression with a high predominance of Corynebacterium, and Corynebacterium promotes inflammation, apoptosis and pyroptosis to inhibit DFU healing.https://doi.org/10.1186/s12879-024-09235-x16S sRNA sequencingBacterial infectionCorynebacteriumDiabetic foot ulcerImmune |
| spellingShingle | Hailong Zheng Han Na Jiangling Yao Sheng Su Feng Han Xiaoyan Li Xiaopan Chen 16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer BMC Infectious Diseases 16S sRNA sequencing Bacterial infection Corynebacterium Diabetic foot ulcer Immune |
| title | 16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer |
| title_full | 16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer |
| title_fullStr | 16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer |
| title_full_unstemmed | 16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer |
| title_short | 16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer |
| title_sort | 16s rrna seq identified corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer |
| topic | 16S sRNA sequencing Bacterial infection Corynebacterium Diabetic foot ulcer Immune |
| url | https://doi.org/10.1186/s12879-024-09235-x |
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