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Population dynamics of an Escherichia coli ST131 lineage during recurrent urinary tract infection.

ABSTRACT: Recurrent urinary tract infections (rUTIs) are extremely common, with ~?25% of all women experiencing a recurrence within 1 year of their original infection. Escherichia coli ST131 is a globally dominant multidrug resistant clone associated with high rates of rUTI. Here, we show the dynamics of an ST131 population over a 5-year period from one elderly woman with rUTI since the 1970s. Using whole genome sequencing, we identify an indigenous clonal lineage (P1A) linked to rUTI and persistence in the fecal flora, providing compelling evidence of an intestinal reservoir of rUTI. We also show that the P1A lineage possesses substantial plasmid diversity, resulting in the coexistence of antibiotic resistant and sensitive intestinal isolates despite frequent treatment. Our longitudinal study provides a unique comprehensive genomic analysis of a clonal lineage within a single individual and suggests a population-wide resistance mechanism enabling rapid adaptation to fluctuating antibiotic exposure.

SUBMITTER: Forde BM

PROVIDER: S-EPMC6692316 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Population dynamics of an Escherichia coli ST131 lineage during recurrent urinary tract infection.

Forde Brian M BM Roberts Leah W LW Phan Minh-Duy MD Peters Kate M KM Fleming Brittany A BA Russell Colin W CW Lenherr Sara M SM Myers Jeremy B JB Barker Adam P AP Fisher Mark A MA Chong Teik-Min TM Yin Wai-Fong WF Chan Kok-Gan KG Schembri Mark A MA Mulvey Matthew A MA Beatson Scott A SA

Nature communications 20190813 1

Recurrent urinary tract infections (rUTIs) are extremely common, with ~ 25% of all women experiencing a recurrence within 1 year of their original infection. Escherichia coli ST131 is a globally dominant multidrug resistant clone associated with high rates of rUTI. Here, we show the dynamics of an ST131 population over a 5-year period from one elderly woman with rUTI since the 1970s. Using whole genome sequencing, we identify an indigenous clonal lineage (P1A) linked to rUTI and persistence in t ...[more]

PMID: 31409795

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Project description:IntroductionRecurrent urinary tract infections (RUTIs) caused by uropathogenic Escherichia coli are costly public health problems impacting patients' quality of life.AimIn this work, a comparative genomics analysis of three clinical RUTI strains isolated from bladder biopsy specimens was performed.Materials and methodsOne hundred seventy-two whole genomes of urinary tract E. coli strains were selected from the NCBI database. The search for virulence factors, fitness genes, regions of interest, and genetic elements associated with resistance was manually carried out. The phenotypic characterization of antibiotic resistance, haemolysis, motility, and biofilm formation was performed. Moreover, adherence and invasion assays with human bladder HTB-5 cells, and transmission electron microscopy (TEM) were performed.ResultsThe UTI-1_774U and UTI-3_455U/ST1193 strains were associated with the extraintestinal pathotypes, and the UTI-2_245U/ST295 strain was associated with the intestinal pathotype, according to a phylogenetic analysis of 172 E. coli urinary strains. The three RUTI strains were of clinical, epidemiological, and zoonotic relevance. Several resistance genes were found within the plasmids of these strains, and a multidrug resistance phenotype was revealed. Other virulence genes associated with CFT073 were not identified in the three RUTI strains (genes for type 1 and P fimbriae, haemolysin hlyA, and sat toxin). Quantitative adherence analysis showed that UTI-1_774U was significantly (p < 0.0001) more adherent to human bladder HTB-5 cells. Quantitative invasion analysis showed that UTI-2_245U was significantly more invasive than the control strains. No haemolysis or biofilm activity was detected in the three RUTI strains. The TEM micrographs showed the presence of short and thin fimbriae only in the UTI-2_245U strain.ConclusionThe high variability and genetic diversity of the RUTI strains indicate that are a mosaic of virulence, resistance, and fitness genes that could promote recurrence in susceptible patients.

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Population dynamics of an Escherichia coli ST131 lineage during recurrent urinary tract infection.

Publications

Population dynamics of an Escherichia coli ST131 lineage during recurrent urinary tract infection.

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