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从糖尿病足溃疡中分离的 菌株的毒力和炎症反应的新见解。

New insight into the virulence and inflammatory response of strains isolated from diabetic foot ulcers.

机构信息

Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.

Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China.

出版信息

Front Cell Infect Microbiol. 2023 Jul 28;13:1234994. doi: 10.3389/fcimb.2023.1234994. eCollection 2023.

DOI:10.3389/fcimb.2023.1234994
PMID:37577369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10416727/
Abstract

strains isolated from diabetic foot ulcers (DFUs) have less virulence, but still cause severe infections. Furthermore, hypovirulent strains appear to be localized in the deep tissues of diabetic foot osteomyelitis, indicating that the unique environment within DFUs affects the pathogenicity of . In this study, the cell-free culture medium (CFCM) of strains isolated from DFUs exhibited higher cytotoxicity to human erythrocytes than those isolated from non-diabetic patients with sepsis or wounds. Among these strains isolated from DFUs, β-toxin negative strains have less virulence than β-toxin positive strains, but induced a higher expression of inflammatory cytokines. Our study and previous studies have shown that the synergistic effect of phenol-soluble modulin α and β-toxin contributes to the higher hemolytic activity of β-toxin positive strains. However, lysis of human erythrocytes by the CFCM of β-toxin negative strains was greatly inhibited by an autolysin inhibitor, sodium polyanethole sulfonate (SPS). A high level of glucose greatly reduced the hemolytic activity of , but promoted the expression of interleukin-6 (IL-6) in human neutrophils. However, 5 mM glucose or glucose-6-phosphate (G6P) increased the hemolytic activity of SA118 (a β-toxin negative strain) isolated from DFUs. Additionally, patients with DFUs with growth of had lower level of serum IL-6 than those with other bacteria, and the CFCM of strains significantly reduced lipopolysaccharide-induced IL-6 expression in human neutrophils. Therefore, the virulence and inflammatory response of strains isolated from DFUs are determined by the levels of glucose and its metabolites, which may explain why it is the predominant bacteria isolated from DFUs.

摘要

从糖尿病足溃疡(DFU)中分离出的菌株毒力较低,但仍会引起严重感染。此外,低毒力菌株似乎局限于糖尿病足骨髓炎的深部组织,表明 DFU 中的独特环境会影响 的致病性。在这项研究中,从 DFU 中分离出的 菌株的无细胞培养上清液(CFCM)对人红细胞的细胞毒性高于从非糖尿病败血症或创伤患者中分离出的菌株。在从 DFU 中分离出的这些 菌株中,β-毒素阴性菌株的毒力低于β-毒素阳性菌株,但诱导的炎症细胞因子表达更高。我们的研究和以前的研究表明,酚可溶性调节素α和β-毒素的协同作用导致β-毒素阳性菌株具有更高的溶血活性。然而,β-毒素阴性菌株的 CFCM 对人红细胞的裂解作用被自溶素抑制剂聚阴离子对甲苯磺酸钠(SPS)大大抑制。高浓度的葡萄糖大大降低了 的溶血活性,但促进了人中性粒细胞中白细胞介素 6(IL-6)的表达。然而,5 mM 葡萄糖或葡萄糖-6-磷酸(G6P)增加了从 DFU 中分离出的 SA118(β-毒素阴性菌株)的溶血活性。此外,DFU 患者中生长的 产生的血清 IL-6 水平低于其他细菌,且 菌株的 CFCM 显著降低了脂多糖诱导的人中性粒细胞中 IL-6 的表达。因此,从 DFU 中分离出的 菌株的毒力和炎症反应由葡萄糖及其代谢物的水平决定,这可能解释了为什么它是从 DFU 中分离出的主要细菌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f0/10416727/d266adb2fa08/fcimb-13-1234994-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f0/10416727/d266adb2fa08/fcimb-13-1234994-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f0/10416727/d78a6f68752f/fcimb-13-1234994-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f0/10416727/e96b46e7663a/fcimb-13-1234994-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f0/10416727/48aed3d7f91f/fcimb-13-1234994-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f0/10416727/3df0761d1506/fcimb-13-1234994-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f0/10416727/d266adb2fa08/fcimb-13-1234994-g007.jpg

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