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细胞外基质刚度对细菌菌落生长及药物抗性的影响
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国家重点研发计划(2022YFD1801103);国家自然科学基金(32202864);北京市教育委员会科学研究计划(KM202310020006);北京市科学技术协会青年人才托举工程(BYESS2023192);市属高校分类发展都市农林特色教师队伍建设项目(11000024T000002961733)


Extracellular matrix stiffness influences colony growth and antibiotic resistance of bacteria
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    【背景】病原体侵入宿主细胞的感染过程受到许多因素调控,其中细胞外基质刚度是宿主细胞普遍具备并调控细胞功能的重要因素,然而其是否对病原菌侵袭宿主细胞后的生长产生影响仍不明确。【目的】探讨细胞外基质刚度对细菌菌落生长、群体结构及抗生素敏感性的影响。【方法】通过聚丙烯酰胺凝胶模拟不同的细胞外基质刚度,观察并分析细菌在不同刚度基底上的菌落形成情况。利用显微镜对培养的菌落进行观察,并通过软件处理图像进一步分析研究结果。【结果】细胞外基质刚度大的情况下细菌菌落生长较大;使用抗生素后细菌菌落边缘密度更容易在细胞外基质刚度较小的聚丙烯酰胺凝胶上变小,而不易在细胞外基质刚度较大的类组织水凝胶上变小。【结论】细胞外基质刚度的增加促进了细菌的黏附和菌落形成,进而改变药物渗透和细菌存活率。研究细胞外基质刚度在细菌生长和药物抗性中的作用机制,对于开发新型抗菌治疗策略具有重要意义。

    Abstract:

    [Background] The process of pathogen invasion into host cells is regulated by various factors, among which extracellular matrix stiffness is a key factor that modulates host cell functions. However, the influence of extracellular matrix stiffness on the growth of pathogens after they invade host cells remains unclear. [Objective] To investigate how extracellular matrix stiffness affects colony growth, population structure, and antibiotic sensitivity of bacteria. [Methods] Polyacrylamide gels were used to mimic varying degrees of extracellular matrix stiffness, and bacterial colony formation on substrates of different stiffness was observed and analyzed. Microscopy was used for observation of bacterial colonies, and image processing software was employed for further analysis. [Results] Bacterial colonies grew larger in the case of higher extracellular matrix stiffness. After the application of antibiotics, the density at the edges of bacterial colonies was more likely to decrease on polyacrylamide gels with lower extracellular matrix stiffness, whereas it was less likely to decrease on tissue-like hydrogels with higher extracellular matrix stiffness. [Conclusion] An increase in extracellular matrix stiffness promotes bacterial adhesion and colony formation, which alters antibiotic penetration and bacterial survival. Understanding the role of matrix stiffness in the growth and antibiotic resistance of bacteria is crucial for developing new antimicrobial treatment strategies.

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卞洋洋,吕若一,张文静,李卓,张朝晖,蔡子雯,孙志刚,刘晓晔. 细胞外基质刚度对细菌菌落生长及药物抗性的影响[J]. 微生物学通报, 2025, 52(6): 2854-2866

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  • 收稿日期:2024-09-16
  • 最后修改日期:2024-11-30
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  • 在线发布日期: 2025-06-20
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