Background

Klebsiella pneumoniae is a gram-negative opportunistic pathogen that causes diseases mostly in immunocompromised individuals. Recently, hypervirulent K. pneumoniae strains also cause severe disease in healthy individuals. Capsular polysaccharide (CPS) is the major virulence determinant in hypervirulent K. pneumoniae and protects the cell against the bactericidal activity of the immune system. Gallic acid (GA), a natural phenolic compound, is known to exhibit wide spectrum antibacterial activity; however, its effect on hypervirulent K. pneumoniae remains largely unresolved. We aimed to identify the effects of GA on CPS biosynthesis in hypervirulent K. pneumoniae.

Methods

Antibacterial activity of GA was evaluated by counting colonies. CPS amount was determined by glucuronic acid content. The transcriptions of cps gene cluster were measured by quantitative real time PCR (qRT-PCR) and the β-galactosidase activity. The effect of GA on the resistance of K. pneumoniae to streptonigrin (SNG), an iron-activated antibiotic, was evaluated. The effect of GA on the resistance of K. pneumoniae to serum killing and phagocytosis by macrophages was observed.

Results

GA inhibited the growth and CPS biosynthesis in K. pneumoniae. GA may affect the iron availability in K. pneumoniae, thus possibly repressing the cps transcription. In addition, GA reduced the resistance of K. pneumoniae to serum killing and enhanced its susceptibility to phagocytosis.

Conclusion

GA possesses bactericidal activity and inhibits the CPS biosynthesis in hypervirulent K. pneumoniae, thereby facilitating pathogen clearance by the host immune system. Therefore, GA may represent a promising strategy for the prevention or treatment of patients with hypervirulent K. pneumoniae infections.

中文翻译：

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没食子酸对肺炎克雷伯菌荚膜多糖生物合成的影响

背景

肺炎克雷伯菌是一种革兰氏阴性机会致病菌，主要在免疫功能低下的个体中引起疾病​​。最近，超强毒力肺炎克雷伯菌菌株也在健康个体中引起严重疾病。荚膜多糖 (CPS) 是高毒性肺炎克雷伯菌的主要毒力决定因子，可保护细胞免受免疫系统的杀菌活性。已知没食子酸 (GA) 是一种天然酚类化合物，具有广谱抗菌活性；然而，它对高毒力肺炎克雷伯菌的影响在很大程度上仍未得到解决。我们的目的是确定 GA 对高毒力肺炎克雷伯菌中 CPS 生物合成的影响。

方法

GA的抗菌活性通过菌落计数来评价。CPS 量由葡萄糖醛酸含量决定。通过定量实时 PCR (qRT-PCR) 和 β-半乳糖苷酶活性测量cps基因簇的转录。评估了 GA 对肺炎克雷伯菌对铁激活抗生素链黑霉素 (SNG) 的耐药性的影响。观察赤霉素对肺炎克雷伯菌对巨噬细胞血清杀伤和吞噬作用的抵抗力的影响。

结果

GA抑制肺炎克雷伯菌的生长和CPS的生物合成。GA 可能影响K. pneumoniae中铁的可用性，从而可能抑制cps转录。此外，GA 降低了肺炎克雷伯菌对血清杀伤的抵抗力并增强了其对吞噬作用的易感性。

结论

GA 具有杀菌活性并抑制高毒力肺炎克雷伯菌中 CPS 的生物合成，从而促进宿主免疫系统清除病原体。因此，GA 可能是预防或治疗高毒力肺炎克雷伯菌感染患者的一种有前途的策略。