Characterization of the Entner-Douderoff Pathway inPseudomonas aeruginosaCatheter-associated Urinary Tract Infections

Author:

Husseini Nour El,Mekonnen Solomon A.,Hall Cherisse L.,Cole Stephanie J.,Carter Jared A.,Belew Ashton T.,El-Sayed NajibORCID,Lee Vincent T.ORCID

Abstract

AbstractPseudomonas aeruginosais an opportunistic nosocomial pathogen responsible for catheter-associated urinary tract infections (CAUTI). In a murine model ofP. aeruginosaCAUTI, we previously demonstrated that urea within urine suppresses quorum sensing and induces the Entner-Douderoff (E-D) pathway. The E-D pathway consists of the geneszwf, pgl, edd, andeda. Zwf and Pgl convert glucose-6-phosphate into 6-phosphogluconate. Edd hydrolyzes 6-phosphogluconate to 2-keto-3-deoxy-6-phosphogluconate (KDPG). Finally, Eda cleaves KDPG to glyceraldehyde-3-phosphate and pyruvate, which enters the citric acid cycle. Here, we generated in-frame E-D mutants in strain PA14 and assessed their growth phenotypes on chemically defined media. These E-D mutants have a growth defect when grown on glucose or gluconate as sole carbon source which are similar to results previously reported for PAO1 mutants lacking E-D genes. RNA-sequencing following short exposure to urine revealed minimal gene regulation differences compared to the wild type. In a murine CAUTI model, virulence testing of E-D mutants revealed that two mutants lackingzwfandpglshowed minor fitness defects. Infection with the Δpglstrain exhibited a 20% increase in host survival, and the Δzwfstrain displayed decreased colonization of the catheter and kidneys. Consequently, our findings suggest that the E-D pathway inP. aeruginosais dispensable in this model of CAUTI.ImportancePrior studies have shown that the Entner-Douderoff pathway is up-regulated whenPseudomonas aeruginosais grown in urine. Pseudomonads use the Entner-Douderoff pathway to metabolize glucose instead of glycolysis which led us to ask whether this pathway is required for urinary tract infection. Here, single-deletion mutants of each gene in the pathway were tested for growth on chemically defined media with single-carbon sources as well as complex media. The effect of each mutant on global gene expression in laboratory media and urine was characterized. The virulence of these mutants in a murine model of catheter-associated urinary tract infection revealed that these mutants had similar levels of colonization indicating that glucose is not the primary carbon source utilized in the urinary tract.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3