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Virulence potential of a multidrug-resistant Escherichia coli belonging to the emerging clonal group ST101-B1 isolated from bloodstream infection

View ORCID ProfileAna Carolina de Mello Santos, View ORCID ProfileRosa Maria Silva, Tiago Barcelos Valiatti, View ORCID ProfileFernanda Fernandes dos Santos, View ORCID ProfileRodrigo Cayô, View ORCID ProfileAna Paula Streling, Carolina Silva Nodari, Ana Cristina Gales, View ORCID ProfileMilton Yutaka Nishiyama-Junior, Eneas Carvalho, Tânia Aparecida Tardelli Gomes
doi: https://doi.org/10.1101/797928
Ana Carolina de Mello Santos
Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), Disciplina de Microbiologia, Departamento de Microbiologia, Imunologia e Parasitologia - DMIP, São Paulo - SP, Brazil
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  • For correspondence: carolina.mello@unifesp.br
Rosa Maria Silva
Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), Disciplina de Microbiologia, Departamento de Microbiologia, Imunologia e Parasitologia - DMIP, São Paulo - SP, Brazil
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Tiago Barcelos Valiatti
Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), Disciplina de Microbiologia, Departamento de Microbiologia, Imunologia e Parasitologia - DMIP, São Paulo - SP, Brazil
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Fernanda Fernandes dos Santos
Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), Disciplina de Microbiologia, Departamento de Microbiologia, Imunologia e Parasitologia - DMIP, São Paulo - SP, Brazil
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Rodrigo Cayô
Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), Disciplina de Microbiologia, Departamento de Microbiologia, Imunologia e Parasitologia - DMIP, São Paulo - SP, BrazilUniversidade Federal de São Paulo - UNIFESP, Laboratório de Imunologia e Bacteriologia - LIB, Setor de Biologia Molecular, Microbiologia e Imunologia, Departamento de Ciências Biológicas - CDB, Instituto de Ciências Ambientais, Químicas e Farmacêuticas - ICAQF, Diadema - SP, Brazil
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Ana Paula Streling
Universidade Federal de São Paulo - UNIFESP, Laboratório Alerta, Disciplina de Infectologia, Departamento de Medicina, Escola Paulista de Medicina - EPM, São Paulo - SP, Brazil
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Carolina Silva Nodari
Universidade Federal de São Paulo - UNIFESP, Laboratório Alerta, Disciplina de Infectologia, Departamento de Medicina, Escola Paulista de Medicina - EPM, São Paulo - SP, Brazil
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Ana Cristina Gales
Universidade Federal de São Paulo - UNIFESP, Laboratório Alerta, Disciplina de Infectologia, Departamento de Medicina, Escola Paulista de Medicina - EPM, São Paulo - SP, Brazil
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Milton Yutaka Nishiyama-Junior
Laboratório Especial de Toxinologia Aplicada – Instituti Butantan, São Paulo – SP, Brazil
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Eneas Carvalho
Laboratório de Bacteriologia - Instituto Butantan, São Paulo - SP, Brazil
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Tânia Aparecida Tardelli Gomes
Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), Disciplina de Microbiologia, Departamento de Microbiologia, Imunologia e Parasitologia - DMIP, São Paulo - SP, Brazil
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Abstract

Escherichia coli EC121 is a multidrug-resistant (MDR) strain isolated from bloodstream infection of an inpatient with persistent gastroenteritis and Zone T lymphoma that died due to septic shock. Despite causing an extraintestinal infection, strain EC121 harbors very few known virulence factors associated with extraintestinal pathogenic E. coli (ExPEC). Furthermore, this strain was assigned to phylogenetic group B1, which is usually related to commensals or diarrheagenic E. coli (DEC) strains, being rarely linked to extraintestinal infections. The question rises if E. coli EC121 is opportunistic or does have a true virulence potential. To address this question the genome of strain EC121 was sequenced, and an in vitro characterization of some pathogenic-associated properties was performed. The data retrieved from genome analyses showed that E. coli strain EC121 belongs to the O154:H25 serotype, and to the sequence type 101-B1 (ST101-B1), which has been epidemiologically linked to extraintestinal infections and antimicrobial resistance spread as well. Moreover, it is shown to be closely related to Shiga-toxin producing E. coli (STEC). Besides, strain EC121 is an MDR strain harboring 14 antimicrobial resistance genes, including blaCTX-M-2, and more than 50 complete virulence genetic clusters, which are reported to be associated either with DEC or ExPEC, or both. Strain EC121 also displays the capacity to adhere to and invade HeLa cells, intestinal Caco-2 cells and bladder T24 cells, as well as the ability to form biofilms on abiotic surfaces, and survive the bactericidal serum complement activity. Altogether, the genetic and phenotypic traits presented by E. coli EC121 may be unveiling a pathogen powered by its multi-drug resistance characteristic. The recognition of such MDR pathogens makes it essential to carry out studies providing accurate information about their virulence potential. Such studies will help in the development of alternative therapies of infection management and spread control of MDR strains.

Author summary Extraintestinal pathogenic Escherichia coli are mostly associated with phylogenetic group B2 and the majority of the studies regarding extraintestinal infection focus on the most virulent strains, which might also possess multidrug-resistant phenotype, like the ST131 strains. On the other hand, strains that belong to phylogroup B1 and are isolated from extraintestinal infections are almost neglected, being considered as merely opportunist pathogens, and the majority of studies reporting strains from this phylogroup focus on antimicrobial resistance. We concentrated our research on one multidrug-resistant strain isolated from bloodstream infection that belongs to phylogenetic group B1 to enlarge the knowledge about the virulence of this kind of strain. We demonstrated that strain EC121 has full potential to be considered a pathogenic strain, because it adheres to and invades intestinal and bladder human cells and survives in human serum; moreover, our data highlight some important EC121 features, which are typical of ST101 strains, like its involvement in the spread of antimicrobial resistance genes, its relationship with extraintestinal infections from diverse sources, and its close relatedness to Shiga toxin-producing E. coli. All these data are important for the development of global actions concerning the spread of antimicrobial resistance, as well as to elucidate the virulence potential of strains that at first glance may be considered as a mere opportunist.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 08, 2019.
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Virulence potential of a multidrug-resistant Escherichia coli belonging to the emerging clonal group ST101-B1 isolated from bloodstream infection
Ana Carolina de Mello Santos, Rosa Maria Silva, Tiago Barcelos Valiatti, Fernanda Fernandes dos Santos, Rodrigo Cayô, Ana Paula Streling, Carolina Silva Nodari, Ana Cristina Gales, Milton Yutaka Nishiyama-Junior, Eneas Carvalho, Tânia Aparecida Tardelli Gomes
bioRxiv 797928; doi: https://doi.org/10.1101/797928
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Virulence potential of a multidrug-resistant Escherichia coli belonging to the emerging clonal group ST101-B1 isolated from bloodstream infection
Ana Carolina de Mello Santos, Rosa Maria Silva, Tiago Barcelos Valiatti, Fernanda Fernandes dos Santos, Rodrigo Cayô, Ana Paula Streling, Carolina Silva Nodari, Ana Cristina Gales, Milton Yutaka Nishiyama-Junior, Eneas Carvalho, Tânia Aparecida Tardelli Gomes
bioRxiv 797928; doi: https://doi.org/10.1101/797928

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