Control of Klebsiella capsule biosynthesis and attachment

克雷伯菌荚膜生物合成和附着的控制

• 批准号: 10713888
• 负责人: Laura Anzaldi Mike
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713888
• 关键词: Adherence; Amoeba genus; Anabolism; Area; Bacteria; Bacteriophages; Cell surface; Cells; Complex; Dehydration; Endogenous Factors; Environment; Environmental Protection; Epithelial Cells; Escherichia coli; Exogenous Factors; Foundations; Gastrointestinal tract structure; Genes; Genetic; Goals; Gram-Negative Bacteria; Heterogeneity; Human; Immune Evasion; Intervention; Klebsiella; Laboratories; Membrane; Metabolic; Metabolism; Microbial Biofilms; Modeling; Nutrient; Polysaccharides; Population; Predatory Behavior; Predisposition; Process; Production; Research; Sewage; Shapes; Signal Transduction; Soil; Source; Surface; Vision; bacterial fitness; capsule; environmental change; environmental stressor; extracellular; fitness; flexibility; gut bacteria; gut colonization; pressure; programs; response; ultraviolet irradiation

SUMMARY Capsular polysaccharide (CPS) is the outermost barrier between bacteria and their environment. It shapes bacterial interactions with external factors, including adherence to surfaces (e.g. biofilm formation, epithelial cell association); protection from environmental stressors (e.g., dehydration, UV irradiation); susceptibility to predation (e.g., phage, bacteria, or amoeba); or immune evasion (e.g. opsonophagocytosis). The Klebsiella species complex is comprised of non-fastidious Gram-negative bacteria that colonize diverse environments, including soil, sewage, sink drains, and mammalian guts. Klebsiella are early colonizers of the human gastrointestinal tract and, when environmental conditions shift in the gut, they have the potential to bloom and out-compete all other colonizers, including closely related Enterobacterales such as E. coli. Clearly, Klebsiella metabolic capacity is robust and flexible. Moreover, Klebsiella CPS production is required for efficient gut colonization and persistence. There is a major gap in our understanding of how exogenous signals are transduced through Klebsiella metabolism and intracellular regulatory networks to control CPS production and how that CPS is attached to the outer envelope. Our long-term goal is to understand how bacterial control of CPS biosynthesis and attachment shapes fitness in response to changing environmental pressures at both single cell and population levels. The objective of this application is to establish a model of the exogenous and endogenous factors that control Klebsiella CPS biosynthesis and cell surface attachment. We seek to establish a framework for understanding how Klebsiella and other Gram- negative bacteria integrate exogenous nutrient signals with their metabolic and regulatory networks to hone their fitness under varying environmental pressures. Recent progress in the laboratory has identified specific genes and some environmental signals that alter CPS attachment and abundance. Our proposed project areas are to examine (1) the mechanisms controlling CPS attachment and release at the outer membrane and (2) how external nutrient sources and cellular metabolism regulate CPS biosynthesis. The overall vision of our research program is to develop a model of how extracellular signals combined with genetic and regulatory heterogeneity create dynamic surface exposed glycans within a bacterial population to enhance overall fitness in the face of environmental challenges. This will provide the foundation for identifying potential intervention points that could be targeted to modulate bacterial CPS production and decolonize specific niches.

概括 囊囊多糖（CPS）是细菌与其环境之间的最外部障碍。它 与外部因素相互作用形成细菌相互作用，包括遵守表面（例如生物膜 形成，上皮细胞缔合）；防止环境压力源（例如脱水，紫外线 辐照）；对捕食的敏感性（例如噬菌体，细菌或变形虫）；或免疫逃避（例如 调查性吞噬作用）。克雷伯氏菌种子综合体由非养革兰氏革兰氏体阴性组成 在包括土壤，污水，水槽排水和哺乳动物肠道在内的各种环境的细菌。 克雷伯氏菌是人类胃肠道的早期殖民者，当环境条件下 肠道转移，他们有可能开花并超越所有其他殖民者，包括紧密的殖民者 相关的肠杆菌，例如大肠杆菌。显然，克雷伯菌的代谢能力强大且灵活。 此外，需要有效的肠道定植和持久性需要克雷伯氏菌CPS产生。有 我们了解如何通过klebsiella转导的外源信号的主要差距 代谢和细胞内调节网络，以控制CPS的产生以及CPS的方式 附着在外部信封上。我们的长期目标是了解CP的细菌控制 生物合成和依恋形状适应性，以应对两者的环境压力的变化 单细胞和人群水平。此应用的目的是建立一个模型 控制克雷伯氏菌CPS生物合成和细胞表面的外源和内源性因素 依恋。我们寻求建立一个框架，以了解克雷伯氏菌和其他革兰氏阴性 负细菌将外源营养信号与其代谢和调节网络相结合 在不同的环境压力下磨练自己的健康状况。实验室的最新进展 确定了特定基因和一些改变CPS附着和丰度的环境信号。 我们拟议的项目领域是检查（1）控制CPS附件的机制和 在外膜和（2）外部养分来源和细胞代谢如何调节 CPS生物合成。我们研究计划的总体愿景是开发一个模型，说明细胞外 信号结合遗传和调节异质性创造了动态表面暴露的聚糖 在细菌人群中，面对环境挑战，可以提高整体健康状况。这会 为识别可能针对调节的潜在干预点提供基础 细菌CPS的产生和非殖民地的特定壁ni。