Characterization of FinO/ProQ Protein FovB Encoded on ESBL Plasmids in Uropathogenic Escherichia Coli


Student thesis: Doctoral Thesis

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Award date20 Sept 2023


Urinary tract infections (UTIs) are the most common bacterial infections in humans worldwide and are mainly caused by uropathogenic Escherichia coli (UPEC). The treatment of UTI becomes more challenging because UPEC is associated with multi-drug resistance (MDR) due to high-frequency inadequate treatments.

This project presents the characterization of FovB (formally named YafB), a FinO/ProQ protein encoded on ESBL IncI1α plasmids. FovB was identified through mass spectrometry-based proteomic analysis of E. coli J53 harboring pCTX-M123_C0996 plasmids. A variant of FovB, FopA, was previously identified in Salmonella enterica, where it was believed to regulate plasmid replication. However, this study demonstrates that FovB is involved in host physiology in UPEC.

RNA Immunoprecipitation and Sequencing (RIP-seq) in both non-pathogenic commensal E. coli J53 and uropathogenic CFT073 revealed a large RNA repertoire of FovB, including hundreds of mRNAs and sRNAs. Notably, the global sRNA GcvB was the most abundant among enriched sRNAs (FovB: FinO domain protein interacts with GcvB). Interestingly, FovB competed with Hfq and antagonized the effect of GcvB on its target gene, re-repressing the translation of peptide transporter DppA. Moreover, FovB gave CFT073 a competitive advantage in amino-acid-rich medium and within the urinary tract. In addition, this study identified pleotrophic impact of FovB on the biosynthesis of surface appendages (flagella, curli, and fimbriae) and oxidative stress.

In conclusion, FovB is a mobile global RNA chaperone encoded on ESBL plasmids that has pleiotropic effects on E. coli, including metabolism and virulence. This study provides insightful knowledge into the plasmid-encoded FinO/ProQ RNA chaperone and partially explains the prevalence of MDR plasmids among pathogens.