Genomic epidemiology and antibiotic susceptibility profiling of uropathogenic Escherichia coli among children in the United States

Abstract

Escherichia coli is the most common cause of urinary tract infections (UTIs) in children, and yet the underlying mechanisms of virulence and antibiotic resistance and the overall population structure of the species is poorly understood within this age group. To investigate whether uropathogenic E. coli (UPEC) from children who developed pyelonephritis carried specific genetic markers, we generated whole-genome sequence data for 96 isolates from children with UTIs. This included 57 isolates from children with either radiologically confirmed pyelonephritis or cystitis and 27 isolates belonging to the well-known multidrug-resistant sequence type ST131, selected to investigate their population structure and antibiotic resistance characteristics. We observed a UPEC population structure that is similar to those reported in adults. In comparison with prior investigations, we found that the full pap operon was more common among UPEC from pediatric cases of pyelonephritis. Further, in contrast with recent reports that the P-fimbriae adhesin-encoding papGII allele is substantially more prevalent in invasive UPEC from adults, we found papGII was common to both invasive and non-invasive UPEC from children. Among the set of ST131 isolates from children with UTIs, we found antibiotic resistance was correlated with known genetic markers of resistance, as in adults. Unexpectedly, we observed that fimH30, an allele of the fimbrial gene fimH often used as a proxy to type ST131 isolates into the most drug-resistant subclade C, was carried by some of the subclade A and subclade B isolates, suggesting that the fimH30 allele could confer a selective advantage for UPEC. IMPORTANCE Urinary tract infections (UTIs), which are most often caused by Escherichia coli, are not well studied in children. Here, we examine genetic characteristics that differentiate UTI-causing bacteria in children that either remain localized to the bladder or are involved in more serious kidney infections. We also examine patterns of antibiotic resistance among strains from children that are part of E. coli sequence type 131, a group of bacteria that commonly cause UTIs and are known to have high levels of drug resistance. This work provides new insight into the virulence and antibiotic resistance characteristics of the bacteria that cause UTIs in children.

Keywords: Escherichia coli; P-fimbriae; antibiotic resistance; genome analysis; pyelonephritis; urinary tract infection; virulence.

Fig 1

The presence of the full pap operon associates with pyelonephritis versus cystitis. (A) Maximum-likelihood phylogeny of the 57 isolates from patients with early scan diagnosis (Materials and Methods). Nodes in the phylogeny are colored by the four common sequence types we observed in the sample set. Phylogenetic clades corresponding to the common phylogroups B2 and D are marked. The colored track displays whether isolates were gathered from children diagnosed with cystitis (pink) or pyelonephritis (dark red). (B) Heatmap showing the presence (gray) or absence (white) of 12 pap operon genes in the sequencing data of each isolate. (C) papG carriage and alleles are illustrated for the 57 isolates from our study alongside UPEC from adults, extracted from supplementary files from the (9) study.

Fig 2

Antibiotic resistance among ST131 isolates. (A) Maximum-likelihood phylogeny of 27 ST131 isolates. Asterisks (*) denote MDR isolates. (B) Colored tracks depict the presence of fluoroquinolone resistance-associated alleles for the core genes gyrA and parC, as well as the carriage of bla _CTX-M-15, sul, and dfrA. (C) Heatmap depicting the degree of resistance exhibited by each isolate to six clinically relevant antibiotics using the Sensititre Gram Negative GN4F assay. Lighter colored cells indicate that the isolate is more susceptible to a particular antibiotic at the lowest dosage, whereas a black cell indicates that the isolate exhibits high levels of resistance to even the largest dosage tested. Antibiotic abbreviations: CIP, ciprofloxacin; LVX, levofloxacin; CRO, ceftriaxone; MEM, meropenem; IPM, imipenem; SXT, trimethoprim-sulfamethoxazole.