Differential Afa/Dr fimbriae expression in the multidrug-resistant Escherichia coli ST131 clone

Alvarez-Fraga, Laura, Phan, Minh-Duy, Goh, Kelvin G. K., Nhu, Nguyen Thi Khanh, Hancock, Steven J., Allsopp, Luke P., Peters, Kate M., Forde, Brian M., Roberts, Leah W., Sullivan, Matthew J., Totsika, Makrina, Beatson, Scott A., Ulett, Glen C. and Schembri, Mark A. (2022) Differential Afa/Dr fimbriae expression in the multidrug-resistant Escherichia coli ST131 clone. mBIO, 13 (1). ISSN 2161-2129

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Abstract

Many antibiotic resistant uropathogenic Escherichia coli (UPEC) strains belong to clones defined by their multilocus sequence type (ST), with ST131 being the most dominant. Although we have a good understanding of resistance development to fluoroquinolones and third-generation cephalosporins by ST131, our understanding of the virulence repertoire that has contributed to its global dissemination is limited. Here we show that the genes encoding Afa/Dr fimbriae, a group of adhesins strongly associated with UPEC that cause gestational pyelonephritis and recurrent cystitis, are found in approximately one third of all ST131 strains. Sequence comparison of the AfaE adhesin protein revealed a unique allelic variant carried by 82.9% of afa-positive ST131 strains. We identify the afa regulatory region as a hotspot for the integration of insertion sequence (IS) elements, all but one of which alter afa transcription. Close investigation demonstrated that the integration of an IS1 element in the afa regulatory region leads to increased expression of Afa/Dr fimbriae, promoting enhanced adhesion to kidney epithelial cells and suggesting a mechanism for altered virulence. Finally, we provide evidence for a more widespread impact of IS1 on ST131 genome evolution, suggesting that IS dynamics contribute to strain level microevolution that impacts ST131 fitness. IMPORTANCE E. coli ST131 is the most common antibiotic resistant UPEC clone associated with human urinary tract and bloodstream infections. Understanding the features of ST131 that have driven its global dissemination remains a critical priority if we are to counter its increasing antibiotic resistance. Here, we utilized a large collection of ST131 isolates to investigate the prevalence, regulation, and function of Afa/ Dr fimbriae, a well-characterized UPEC colonization and virulence factor. We show that the afa genes are found frequently in ST131 and demonstrate how the integration of IS elements in the afa regulatory region modulates Afa expression, presenting an example of altered virulence capacity. We also exploit a curated set of ST131 genomes to map the integration of the antibiotic resistance-associated IS1 element in the ST131 pangenome, providing evidence for its widespread impact on ST131 genome evolution.

Item Type: Article
Additional Information: Funding Information: This work was supported by grants APP1181958 and APP2001431 from the National Health and Medical Research Council of Australia (NHMRC). L.A.F. is supported by the Galician Ministry of Culture, Education, and University Planning, and Galician Ministry of Economy, Employment, and Industry (Regional Government of Galicia-Spain) (IN606B-2018/011).
Uncontrolled Keywords: adhesins,antibiotic resistance,fimbriae,uropathogenic escherichia coli,virulence regulation,microbiology,virology ,/dk/atira/pure/subjectarea/asjc/2400/2404
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Depositing User: LivePure Connector
Date Deposited: 15 Aug 2022 11:30
Last Modified: 26 Sep 2022 05:53
URI: https://ueaeprints.uea.ac.uk/id/eprint/87250
DOI: 10.1128/MBIO.03519-21

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