Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniae.

IF 4.5 2区 医学 Q2 IMMUNOLOGY Journal of Microbiology Immunology and Infection Pub Date : 2024-10-24 DOI:10.1016/j.jmii.2024.10.002
Tien-Huang Lin, Chen-Yu Wang, Chien-Chen Wu, Ching-Ting Lin
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Abstract

Background: Klebsiella pneumoniae is a Gram-negative bacterium that can cause infections, especially in individuals with diabetes. Recently, more hypervirulent strains have emerged, posing a threat even to healthy individuals. Understanding how K. pneumoniae regulates its virulence factors is crucial. Acetyl-phosphate (AcP) is essential for bacterial metabolism and can affect virulence factor expression. However, the role of the Pta-AckA pathway, which regulates AcP levels, in K. pneumoniae pathogenesis remains unclear.

Methods: Deletion mutants lacking the pta and ackA, involved in AcP production and hydrolysis, were generated in K. pneumoniae CG43S3. Their effects on AcP levels, the patterns of global acetylated protein, capsular polysaccharide (CPS) amount, serum resistance, type 3 fimbriae expression, biofilm formation, and virulence in G. mellonella larva were assessed.

Results: Deletion of ackA in K. pneumoniae CG43S3 led to AcP accumulation, while pta deletion abolished AcP synthesis when grown in TB7+1 % glucose. This pathway influenced global protein acetylation, with pta deletion decreasing acetylation and ackA deletion increasing it. Additionally, pta deletion decreased the CPS amount, serum resistance, and type 3 fimbriae expression, while ackA deletion increased these factors. Furthermore, deleting pta and ackA attenuated the infected larva's virulence and death rate.

Conclusion: Our findings highlight the critical role of the Pta-AckA pathway in K. pneumoniae pathogenesis. This pathway regulates AcP levels, global protein acetylation, CPS production, serum resistance, and type 3 fimbriae expression, ultimately impacting virulence. The information provides insights into potential therapeutic targets for combating K. pneumoniae infection.

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肺炎克雷伯氏菌中 Pta-AckA 通路对 CPS 生物合成和 3 型纤毛膜表达的影响。
背景:肺炎克雷伯菌是一种革兰氏阴性菌,可引起感染,尤其是糖尿病患者。最近,出现了更多的高毒力菌株,甚至对健康人也构成了威胁。了解肺炎克氏菌如何调节其毒力因子至关重要。乙酰磷酸(AcP)对细菌的新陈代谢至关重要,并可影响毒力因子的表达。然而,调节 AcP 水平的 Pta-AckA 通路在肺炎双球菌致病过程中的作用仍不清楚:方法:在肺炎双球菌 CG43S3 中产生了缺失参与 AcP 生成和水解的 pta 和 ackA 的缺失突变体。方法:在肺炎双球菌 CG43S3 中产生了缺乏 pta 和 ackA 的缺失突变体,它们参与 AcP 的产生和水解,评估了它们对 AcP 水平、全局乙酰化蛋白模式、荚膜多糖(CPS)量、血清抗性、3 型缘毛表达、生物膜形成和对 G. mellonella 幼虫的毒力的影响:结果:当肺炎克氏菌 CG43S3 在 TB7+1 % 葡萄糖中生长时,ackA 的缺失会导致 AcP 的积累,而 pta 的缺失则会阻碍 AcP 的合成。这一途径影响了全局蛋白质乙酰化,pta 缺失会降低乙酰化,ackA 缺失则会增加乙酰化。此外,pta 缺失会减少 CPS 量、血清抗性和 3 型叶状体的表达,而 ackA 缺失则会增加这些因素。此外,缺失 pta 和 ackA 会降低受感染幼虫的毒力和死亡率:我们的研究结果凸显了 Pta-AckA 通路在肺炎双球菌致病过程中的关键作用。该途径调控 AcP 水平、全局蛋白乙酰化、CPS 生成、血清抗性和 3 型缘膜表达,最终影响毒力。这些信息提供了抗击肺炎克氏菌感染的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Microbiology Immunology and Infection
Journal of Microbiology Immunology and Infection IMMUNOLOGY-INFECTIOUS DISEASES
CiteScore
15.90
自引率
5.40%
发文量
159
审稿时长
67 days
期刊介绍: Journal of Microbiology Immunology and Infection is an open access journal, committed to disseminating information on the latest trends and advances in microbiology, immunology, infectious diseases and parasitology. Article types considered include perspectives, review articles, original articles, brief reports and correspondence. With the aim of promoting effective and accurate scientific information, an expert panel of referees constitutes the backbone of the peer-review process in evaluating the quality and content of manuscripts submitted for publication.
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