Comprehensive Molecular Characterization of Escherichia coli Isolates from Urine Samples of Hospitalized Patients in Rio de Janeiro, Brazil

ORIGINAL RESEARCH published: 16 February 2018 doi: 10.3389/fmicb.2018.00243 Comprehensive Molecular Characterization of Escherichia coli Isolates from Urine Samples of Hospitalized Patients in Rio de Janeiro, Brazil Ana Carolina C. Campos 1,2 , Nathália L. Andrade 1 , Mithila Ferdous 2 , Monika A. Chlebowicz 2 , Carla C. Santos 3 , Julio C. D. Correal 1,3 , Jerome R. Lo Ten Foe 2 , Ana Cláudia P. Rosa 1 , Paulo V. Damasco 4,5 , Alex W. Friedrich 2 and John W. A. Rossen 2* 1 Edited by: Jorge Blanco, Universidade de Santiago de Compostela, Spain Reviewed by: Vanesa García, Universidade de Santiago de Compostela, Spain María de Toro, Centro de Investigación Biomédica de La Rioja, Spain *Correspondence: John W. A. Rossen Specialty section: This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology Received: 22 September 2017 Accepted: 31 January 2018 Published: 16 February 2018 Citation: Campos ACC, Andrade NL, Ferdous M, Chlebowicz MA, Santos CC, Correal JCD, Lo Ten Foe JR, Rosa ACP, Damasco PV, Friedrich AW and Rossen JWA (2018) Comprehensive Molecular Characterization of Escherichia coli Isolates from Urine Samples of Hospitalized Patients in Rio de Janeiro, Brazil. Front. Microbiol. 9:243. doi: 10.3389/fmicb.2018.00243 Departamento de Microbiologia, Imunologia e Parasitologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil, 2 Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands, 3 Departamento de Controle de Infecções, Hospital Rio Laranjeiras, Rio de Janeiro, Brazil, 4 Departamento de Doenças Infecciosas e Parasitárias, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil, 5 Departamento de Doenças Infecciosas e Parasitárias, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil Urinary tract infections (UTIs) are often caused by Escherichia coli. Their increasing resistance to broad-spectrum antibiotics challenges the treatment of UTIs. Whereas, E. coli ST131 is often multidrug resistant (MDR), ST69 remains susceptible to antibiotics such as cephalosporins. Both STs are commonly linked to community and nosocomial infections. E. coli phylogenetic groups B2 and D are associated with virulence and resistance profiles making them more pathogenic. Little is known about the population structure of E. coli isolates obtained from urine samples of hospitalized patients in Brazil. Therefore, we characterized E. coli isolated from urine samples of patients hospitalized at the university and three private hospitals in Rio de Janeiro, using whole genome sequencing. A high prevalence of E. coli ST131 and ST69 was found, but other lineages, namely ST73, ST648, ST405, and ST10 were also detected. Interestingly, isolates could be divided into two groups based on their antibiotic susceptibility. Isolates belonging to ST131, ST648, and ST405 showed a high resistance rate to all antibiotic classes tested, whereas isolates belonging to ST10, ST73, ST69 were in general susceptible to the antibiotics tested. Additionally, most ST69 isolates, normally resistant to aminoglycosides, were susceptible to this antibiotic in our population. The majority of ST131 isolates were ESBL-producing and belonged to serotype O25:H4 and the H30-R subclone. Previous studies showed that this subclone is often associated with more complicated UTIs, most likely due to their high resistance rate to different antibiotic classes. Sequenced isolates could be classified into five phylogenetic groups of which B2, D, and F showed higher resistance rates than groups A and B1. No significant difference for the predicted virulence genes scores was found for isolates belonging to ST131, ST648, ST405, and ST69. In contrast, the phylogenetic groups B2, D and F showed a higher predictive virulence score compared to phylogenetic groups A and B1. Frontiers in Microbiology | www.frontiersin.org 1 February 2018 | Volume 9 | Article 243 Campos et al. Characterization of E. coli Causing UTIs In conclusion, despite the diversity of E. coli isolates causing UTIs, clonal groups O25:H4-B2-ST131 H30-R, O1:H6-B2-ST648, and O102:H6-D-ST405 were the most prevalent. The emergence of highly virulent and MDR E. coli in Brazil is of high concern and requires more attention from the health authorities. Keywords: Escherichia coli, urinary tract infections, Brazil, ST131, antibiotic resistance, virulence genes, whole genome sequencing, diagnostic stewardship INTRODUCTION isolates (Katouli, 2010). Moreover, pathogenic ExPEC isolates harbor specific virulence genes which confer their pathogenic potential (Cyoia et al., 2015) and are involved in every step in the pathogenicity of ExPEC. Thus, adhesins are a prerequisite to adherence and successful colonization, toxins are responsible for cell damage to urinary tract epithelial cells, and the iron uptake system allows colonization of the urinary tract thereby helping the bacteria to persist (Alizade et al., 2014). Despite the diversity of ExPEC causing infections, previous studies have shown the connection between specific E. coli lineages and their particular resistance profiles, and severity of the infections (Can et al., 2015; Matsumura et al., 2016; Zhang et al., 2016). Thus, defining the genetic background of the pathogen by the identification of a particular ST, its serotype and the detection of resistance genes, can be useful not only for improving further patient treatment but also to allow an improved risk assessment of bacterial infections in the hospitals. The aim of this study is to comprehensively characterize the population structure of E. coli from urine samples collected from patients in four hospitals in Rio de Janeiro, Brazil using whole genome sequencing (WGS). Urinary Tract Infections (UTIs) are one of the most important causes of community and healthcare-associated infections in many clinical onsets worldwide, including Brazil (Terpstra and Geerlings, 2016; Wurpel et al., 2016). Indeed 30–50% of healthcare-associated infections are due to UTIs. This high prevalence is linked to several risk factors, such as catheterization, surgical manipulation and disruption of the urinary tract, diabetes, immunosuppressant drug use, previous admissions, and other comorbidities (Saltoglu et al., 2015; Redder et al., 2016). The risk factors and antibiotic resistance profiles are different for infections acquired in the community or in the hospital environments (Saltoglu et al., 2015). Although in general the majority of UTI cases are uncomplicated, UTIs in hospitalized patients increase the risk for developing sepsis and lead to higher mortality rates (Melzer and Welch, 2013). Escherichia coli is the main etiological agent responsible for 70–90% of all UTIs (Gurevich et al., 2016; Terpstra and Geerlings, 2016). The treatment of patients with UTIs has become increasingly difficult because of (...truncated)