title: Genomic and Functional Portrait of a Highly Virulent, CTX-M-15-Producing H30-Rx Subclone of Escherichia coli Sequence Type 131.
abstract: Escherichia coli sequence type 131 (ST131) is a pandemic clone associated with multidrug-resistant, extraintestinal infections, attributable to the presence of the CTX-M-15 extended-spectrum β-lactamase gene and mutations entailing fluoroquinolone resistance. Studies on subclones within E. coli ST131 are critically required for targeting and implementation of successful control efforts. Our study comprehensively analyzed the genomic and functional attributes of the H30-Rx subclonal strains NA097 and NA114, belonging to the ST131 lineage. We carried out whole-genome sequencing, comparative analysis, phenotypic virulence assays, and profiling of the antibacterial responses of THP1 cells infected with these subclones. Phylogenomic analysis suggested that the strains were clonal in nature and confined entirely to a single clade. Comparative genomic analysis revealed that the virulence and resistance repertoires were comparable among the H30-Rx ST131 strains except for the commensal ST131 strain SE15. Similarly, seven phage-specific regions were found to be strongly associated with the H30-Rx strains but were largely absent in the genome of SE15. Phenotypic analysis confirmed the virulence and resistance similarities between the two strains. However, NA097 was found to be more robust than NA114 in terms of virulence gene carriage (dra operon), invasion ability (P < 0.05), and antimicrobial resistance (streptomycin resistance). RT(2) gene expression profiling revealed generic upregulation of key proinflammatory responses in THP1 cells, irrespective of ST131 lineage status. In conclusion, our study provides comprehensive, genome-inferred insights into the biology and immunological properties of ST131 strains and suggests clonal diversification of genomic and phenotypic features within the H30-Rx subclone of E. coli ST131.
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Ranjan
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, India.
authors.forename: Sabiha
authors.initials: S
authors.lastname: Shaik
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, India.
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, India.
authors.forename: Nishant
authors.initials: N
authors.lastname: Nandanwar
authors.affiliation: Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany Robert Koch Institute, Berlin, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Semmler
authors.affiliation: Department of Microbiology, D. Y. Patil University, Pimpri, India.
authors.forename: Savita
authors.initials: S
authors.lastname: Jadhav
authors.affiliation: Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany Robert Koch Institute, Berlin, Germany.
authors.forename: Lothar H
authors.initials: LH
authors.lastname: Wieler
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, India niyaz.ahmed@uohyd.ac.in.
authors.forename: Niyaz
authors.initials: N
authors.lastname: Ahmed
mesh_terms: D002460:Cell Line; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D014774:Virulence / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: C473109:beta-lactamase CTX-M-15; D001618:beta-Lactamases