Characterization of the Entner-Douderoff Pathway in Catheter-associated Urinary Tract Infections

Overview

Journal bioRxiv

Date 2023 Nov 28

PMID 38014081

Authors

Nour El Husseini

Solomon A Mekonnen

Cherisse L Hall

Stephanie J Cole

Jared A Carter

Ashton T Belew

Najib El-Sayed

Vincent T Lee

Affiliations

Soon will be listed here.

Abstract

is an opportunistic nosocomial pathogen responsible for catheter-associated urinary tract infections (CAUTI). In a murine model of CAUTI, 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 genes , , , and . 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 lacking and showed minor fitness defects. Infection with the ∆ strain exhibited a 20% increase in host survival, and the ∆ strain displayed decreased colonization of the catheter and kidneys. Consequently, our findings suggest that the E-D pathway in is dispensable in this model of CAUTI.

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