Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131

Escherichia coli associated with urinary tract infections and bacteremia has been intensively investigated, including recent work focusing on the virulent, globally disseminated, multidrug-resistant lineage ST131. To contextualize ST131 within the broader E. coli population associated with disease, we used genomics to analyze a systematic 11-yr hospital-based survey of E. coli associated with bacteremia using isolates collected from across England by the British Society for Antimicrobial Chemotherapy and from the Cambridge University Hospitals NHS Foundation Trust. Population dynamics analysis of the most successful lineages identified the emergence of ST131 and ST69 and their establishment as two of the five most common lineages along with ST73, ST95, and ST12. The most frequently identified lineage was ST73. Compared to ST131, ST73 was susceptible to most antibiotics, indicating that multidrug resistance was not the dominant reason for prevalence of E. coli lineages in this population. Temporal phylogenetic analysis of the emergence of ST69 and ST131 identified differences in the dynamics of emergence and showed that expansion of ST131 in this population was not driven by sequential emergence of increasingly resistant subclades. We showed that over time, the E. coli population was only transiently disturbed by the introduction of new lineages before a new equilibrium was rapidly achieved. Together, these findings suggest that the frequency of E. coli lineages in invasive disease is driven by negative frequency-dependent selection occurring outside of the hospital, most probably in the commensal niche, and that drug resistance is not a primary determinant of success in this niche.

[1]  W. Fitch Toward Defining the Course of Evolution: Minimum Change for a Specific Tree Topology , 1971 .

[2]  M. Inouye,et al.  EcOH: In silico serotyping of E. coli from short read data , 2015, bioRxiv.

[3]  Nicola K. Petty,et al.  Insights into a Multidrug Resistant Escherichia coli Pathogen of the Globally Disseminated ST131 Lineage: Genome Analysis and Virulence Mechanisms , 2011, PloS one.

[4]  Wai Lok Sibon Li,et al.  Accurate model selection of relaxed molecular clocks in bayesian phylogenetics. , 2012, Molecular biology and evolution.

[5]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[6]  L. Price,et al.  The Epidemic of Extended-Spectrum-β-Lactamase-Producing Escherichia coli ST131 Is Driven by a Single Highly Pathogenic Subclone, H30-Rx , 2013, mBio.

[7]  Mark A. Schembri,et al.  The Complete Genome Sequence of Escherichia coli EC958: A High Quality Reference Sequence for the Globally Disseminated Multidrug Resistant E. coli O25b:H4-ST131 Clone , 2014, PloS one.

[8]  Nicola K. Petty,et al.  Evolutionary Adaptation of an AraC-Like Regulatory Protein in Citrobacter rodentium and Escherichia Species , 2015, Infection and Immunity.

[9]  Jacqueline A. Keane,et al.  Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins , 2014, Nucleic acids research.

[10]  C. Mcnulty,et al.  English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) 2010 to 2014: report 2015 , 2015 .

[11]  I. Okeke,et al.  espC Pathogenicity Island of Enteropathogenic Escherichia coli Encodes an Enterotoxin , 2001, Infection and Immunity.

[12]  M. Suchard,et al.  Bayesian Phylogenetics with BEAUti and the BEAST 1.7 , 2012, Molecular biology and evolution.

[13]  Daniel Falush,et al.  Sex and virulence in Escherichia coli: an evolutionary perspective , 2006, Molecular microbiology.

[14]  J. Andrews,et al.  Determination of minimum inhibitory concentrations. , 2001, The Journal of antimicrobial chemotherapy.

[15]  N. Woodford,et al.  Surveillance of antibiotic susceptibility of urinary tract pathogens for a population of 5.6 million over 4 years. , 2015, The Journal of antimicrobial chemotherapy.

[16]  E. Denamur,et al.  The Clermont Escherichia coli phylo-typing method revisited: improvement of specificity and detection of new phylo-groups. , 2013, Environmental microbiology reports.

[17]  K. Paszkiewicz,et al.  Increase in bacteraemia cases in the East Midlands region of the UK due to MDR Escherichia coli ST73: high levels of genomic and plasmid diversity in causative isolates. , 2016, The Journal of antimicrobial chemotherapy.

[18]  Justin Zobel,et al.  SRST2: Rapid genomic surveillance for public health and hospital microbiology labs , 2014, bioRxiv.

[19]  M. Kuskowski,et al.  Temporal Trends in Antimicrobial Resistance and Virulence-Associated Traits within the Escherichia coli Sequence Type 131 Clonal Group and Its H30 and H30-Rx Subclones, 1968 to 2012 , 2014, Antimicrobial Agents and Chemotherapy.

[20]  R. Bonomo,et al.  Complete Sequence of a KPC-Producing IncN Multidrug-Resistant Plasmid from an Epidemic Escherichia coli Sequence Type 131 Strain in China , 2014, Antimicrobial Agents and Chemotherapy.

[21]  Torsten Seemann,et al.  Prokka: rapid prokaryotic genome annotation , 2014, Bioinform..

[22]  Nicola K. Petty,et al.  Global dissemination of a multidrug resistant Escherichia coli clone , 2014, Proceedings of the National Academy of Sciences.

[23]  N. Geva-Zatorsky,et al.  Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species , 2016, Proceedings of the National Academy of Sciences.

[24]  T. Rogers,et al.  Characterization of Escherichia coli bloodstream isolates associated with mortality. , 2016, Journal of medical microbiology.

[25]  O. Clermont,et al.  Rapid and Simple Determination of theEscherichia coli Phylogenetic Group , 2000, Applied and Environmental Microbiology.

[26]  M. Suchard,et al.  Improving the accuracy of demographic and molecular clock model comparison while accommodating phylogenetic uncertainty. , 2012, Molecular biology and evolution.

[27]  Liping Zhang,et al.  Characterization of carbapenemases, extended spectrum β-lactamases, quinolone resistance and aminoglycoside resistance determinants in carbapenem-non-susceptible Escherichia coli from a teaching hospital in Chongqing, Southwest China. , 2014, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[28]  J. Cheesbrough,et al.  Population structure, virulence potential and antibiotic susceptibility of uropathogenic Escherichia coli from Northwest England. , 2012, The Journal of antimicrobial chemotherapy.

[29]  S. Beatson,et al.  UpaH Is a Newly Identified Autotransporter Protein That Contributes to Biofilm Formation and Bladder Colonization by Uropathogenic Escherichia coli CFT073 , 2010, Infection and Immunity.

[30]  David S. Wishart,et al.  PHAST: A Fast Phage Search Tool , 2011, Nucleic Acids Res..

[31]  Andrew J. Page,et al.  Roary: rapid large-scale prokaryote pan genome analysis , 2015, bioRxiv.

[32]  Maliha Aziz,et al.  Abrupt emergence of a single dominant multidrug-resistant strain of Escherichia coli. , 2013, The Journal of infectious diseases.

[33]  M. D. Kraker,et al.  The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveillance System. , 2013, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[34]  Jay Shendure,et al.  Large-scale genomic sequencing of extraintestinal pathogenic Escherichia coli strains , 2015, Genome research.

[35]  A. Rambaut,et al.  BEAST: Bayesian evolutionary analysis by sampling trees , 2007, BMC Evolutionary Biology.

[36]  J. R. Johnson,et al.  Phylogenetic distribution of extraintestinal virulence-associated traits in Escherichia coli. , 2001, The Journal of infectious diseases.

[37]  Jukka Corander,et al.  Hierarchical and Spatially Explicit Clustering of DNA Sequences with BAPS Software , 2013, Molecular biology and evolution.

[38]  Jacques Elion,et al.  The Link between Phylogeny and Virulence inEscherichia coli Extraintestinal Infection , 1999, Infection and Immunity.

[39]  J. Corander,et al.  Identification of enterotoxigenic Escherichia coli (ETEC) clades with long-term global distribution , 2014, Nature Genetics.

[40]  Herbert Schmidt,et al.  Pathogenicity Islands in Bacterial Pathogenesis , 2004, Clinical Microbiology Reviews.

[41]  S. Rasmussen,et al.  Identification of acquired antimicrobial resistance genes , 2012, The Journal of antimicrobial chemotherapy.

[42]  D. G. Moriel,et al.  Functional Heterogeneity of the UpaH Autotransporter Protein from Uropathogenic Escherichia coli , 2012, Journal of bacteriology.

[43]  A. Carattoli,et al.  Identification of plasmids by PCR-based replicon typing. , 2005, Journal of microbiological methods.

[44]  Xavier Bertrand,et al.  Escherichia coli ST131, an Intriguing Clonal Group , 2014, Clinical Microbiology Reviews.

[45]  W. Pirovano,et al.  Toward almost closed genomes with GapFiller , 2012, Genome Biology.

[46]  David J. Edwards,et al.  Evolution of atypical enteropathogenic E. coli by repeated acquisition of LEE pathogenicity island variants , 2016, Nature Microbiology.

[47]  J. Wain,et al.  Population structure of Escherichia coli causing bacteraemia in the UK and Ireland between 2001 and 2010. , 2016, The Journal of antimicrobial chemotherapy.

[48]  L. Journet,et al.  Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut , 2016, Proceedings of the National Academy of Sciences.

[49]  F. Navarro-Garcia,et al.  EspC, an Autotransporter Protein Secreted by Enteropathogenic Escherichia coli, Causes Apoptosis and Necrosis through Caspase and Calpain Activation, Including Direct Procaspase-3 Cleavage , 2016, mBio.

[50]  Walter Pirovano,et al.  BIOINFORMATICS APPLICATIONS , 2022 .

[51]  Robert C. Edgar,et al.  BIOINFORMATICS APPLICATIONS NOTE , 2001 .

[52]  Alexandros Stamatakis,et al.  RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models , 2006, Bioinform..

[53]  J. R. Johnson,et al.  Extended virulence genotypes of Escherichia coli strains from patients with urosepsis in relation to phylogeny and host compromise. , 2000, The Journal of infectious diseases.

[54]  E. Birney,et al.  Velvet: algorithms for de novo short read assembly using de Bruijn graphs. , 2008, Genome research.

[55]  B. Diep,et al.  Clonal Composition and Community Clustering of Drug-Susceptible and -Resistant Escherichia coli Isolates from Bloodstream Infections , 2012, Antimicrobial Agents and Chemotherapy.

[56]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[57]  R. Reynolds,et al.  Survey, laboratory and statistical methods for the BSAC Resistance Surveillance Programmes. , 2008, The Journal of antimicrobial chemotherapy.

[58]  C. Lohse,et al.  The Clonal Distribution and Diversity of Extraintestinal Escherichia coli Isolates Vary According to Patient Characteristics , 2013, Antimicrobial Agents and Chemotherapy.

[59]  P. Gajer,et al.  The Pangenome Structure of Escherichia coli: Comparative Genomic Analysis of E. coli Commensal and Pathogenic Isolates , 2008, Journal of bacteriology.

[60]  D. Rasko,et al.  Genomic diversity of EPEC associated with clinical presentations of differing severity , 2016, Nature Microbiology.

[61]  Andrew J. Page,et al.  Multilocus sequence typing by blast from de novo assemblies against PubMLST , 2016, J. Open Source Softw..

[62]  M. Wilcox,et al.  Escherichia coli bacteraemia: 2 years of prospective regional surveillance (2010-12). , 2014, The Journal of antimicrobial chemotherapy.

[63]  Michael Inouye,et al.  In silico serotyping of E. coli from short read data identifies limited novel O-loci but extensive diversity of O:H serotype combinations within and between pathogenic lineages , 2016, Microbial genomics.

[64]  C. Constantinidou,et al.  Genomic analysis uncovers a phenotypically diverse but genetically homogeneous Escherichia coli ST131 clone circulating in unrelated urinary tract infections. , 2012, The Journal of antimicrobial chemotherapy.

[65]  Olivier Gascuel,et al.  Fast Dating Using Least-Squares Criteria and Algorithms , 2015, Systematic biology.

[66]  Jianzhong Shen,et al.  Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. , 2015, The Lancet. Infectious diseases.

[67]  B. Finlay,et al.  Characterization of EspC, a 110-kilodalton protein secreted by enteropathogenic Escherichia coli which is homologous to members of the immunoglobulin A protease-like family of secreted proteins , 1996, Journal of bacteriology.

[68]  Jon R. Armstrong,et al.  Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[69]  Daniel J. Wilson,et al.  Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131 , 2015, mBio.

[70]  A. McNally,et al.  Multidrug-Resistant Escherichia coli Bacteremia , 2013, Emerging infectious diseases.

[71]  E. Denamur,et al.  Escherichia coli molecular phylogeny using the incongruence length difference test. , 1998, Molecular biology and evolution.

[72]  H. Mobley,et al.  Identification of Sat, an autotransporter toxin produced by uropathogenic Escherichia coli , 2000, Molecular microbiology.

[73]  S. Beatson,et al.  Sequential Acquisition of Virulence and Fluoroquinolone Resistance Has Shaped the Evolution of Escherichia coli ST131 , 2016, mBio.

[74]  Jukka Corander,et al.  Enhanced Bayesian modelling in BAPS software for learning genetic structures of populations , 2008, BMC Bioinformatics.

[75]  Simon R. Harris,et al.  SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments , 2016, bioRxiv.

[76]  R. Skov,et al.  Plasmid-mediated colistin resistance (mcr-1 gene): three months later, the story unfolds. , 2016, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.