山梨糖代谢在酸性条件下增强适应性和毒力中的作用

The Role of -Sorbose Metabolism in Enhancing Fitness and Virulence in Under Acidic Conditions.

作者信息

Qiu Tian, Chen Xudong, Deng Xue, Zhang Guili, Wen Shu'an, Wu Ji, Sun Dandan, Li Tong, Yan Bin, Dai Min, Zhong Lan-Lan, Tian Guo-Bao

机构信息

School of Laboratory Medicine, Chengdu Medical College, Chengdu, 610500, People's Republic of China.

Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.

出版信息

Infect Drug Resist. 2025 Jun 20;18:3071-3086. doi: 10.2147/IDR.S526664. eCollection 2025.

Abstract

BACKGROUND

Pathogenic  ) causes a wide range of infections in humans and animals, imposing a significant global health burden. While metabolic flexibility is critical for  fitness to host environments, the role of secondary carbon sources like -Sorbose remains poorly characterized.

METHODS

The functional importance of -Sorbose metabolism in  CFT073 was investigated under acidic conditions simulating gastrointestinal and urinary tract environments. A Δ mutant, with deletion of a key gene in -Sorbose catabolism, was generated, and its growth, viability, virulence factors, proton motive force (PMF), oxidative stress levels, and transcriptomic profiles under acidic pH (3.5-5.5) were assessed. Virulence was further tested using a  infection model.

RESULTS

Deletion of  caused severe growth defects, loss of virulence factors (flagella and fimbriae), disrupted PMF, and oxidative stress accumulation under acidic conditions. Transcriptomic analysis revealed dysregulation of energy metabolism pathways and downregulation of virulence-associated genes in the Δ mutant. Importantly, -Sorbose metabolism deficiency significantly attenuated bacterial survival at pH 3.5 and reduced virulence in the  model.

CONCLUSION

These findings demonstrate that -Sorbose metabolism is essential for  to maintain energy homeostasis, virulence, and acid resistance. Targeting this pathway may offer a novel therapeutic strategy against pathogenic  infections.

摘要

背景

致病性(此处原文缺失具体病原体名称)在人类和动物中引发多种感染,给全球健康带来重大负担。虽然代谢灵活性对于(此处原文缺失具体病原体名称)适应宿主环境至关重要,但诸如L -山梨糖等次生碳源的作用仍未得到充分表征。

方法

在模拟胃肠道和泌尿道环境的酸性条件下,研究了L -山梨糖代谢在(此处原文缺失具体病原体名称)CFT073中的功能重要性。构建了一个缺失L -山梨糖分解代谢关键基因的Δ(此处原文缺失具体基因名称)突变体,并评估了其在酸性pH(3.5 - 5.5)下的生长、活力、毒力因子、质子动力势(PMF)、氧化应激水平和转录组图谱。使用(此处原文缺失具体感染模型名称)感染模型进一步测试毒力。

结果

缺失(此处原文缺失具体基因名称)导致严重的生长缺陷、毒力因子(鞭毛和菌毛)丧失、PMF破坏以及在酸性条件下氧化应激积累。转录组分析揭示了Δ(此处原文缺失具体基因名称)突变体中能量代谢途径失调和毒力相关基因下调。重要的是,L -山梨糖代谢缺陷显著降低了细菌在pH 3.5时的存活率,并降低了(此处原文缺失具体感染模型名称)模型中的毒力。

结论

这些发现表明,L -山梨糖代谢对于(此处原文缺失具体病原体名称)维持能量稳态、毒力和耐酸性至关重要。针对该途径可能提供一种针对致病性(此处原文缺失具体病原体名称)感染的新型治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b56/12186808/1f3b559a8bc0/IDR-18-3071-g0001.jpg

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