title: Haplotype diversity in "source-sink" dynamics of Escherichia coli urovirulence.
abstract: FimH, the mannose-specific, type 1 fimbrial adhesin of Escherichia coli, acquires amino acid replacements adaptive in extraintestinal niches (the genitourinary tract) but detrimental in the main habitat (the large intestine). This microevolutionary dynamics is reminiscent of an ecological "source-sink" model of continuous species spread from a stable primary habitat (source) into transient secondary niches (sink), with eventual extinction of the sink-evolved populations. Here, we have adapted two ecological analytical tools-diversity indexes DS and alpha--to compare size and frequency distributions of fimH haplotypes between evolutionarily conserved FimH variants ("source" haplotypes) and FimH variants with adaptive mutations (putative "sink" haplotypes). Both indexes show two- to threefold increased diversity of the sink fimH haplotypes relative to the source haplotypes, a pattern that ran opposite to those seen with nonstructural fimbrial genes (fimC and fimI) and housekeeping loci (adk and fumC) but similar to that seen with another fimbrial adhesin of E. coli, papG-II, also implicated in extraintestinal infections. The increased diversity of the sink pool of adhesin genes is due to the increased richness of the haplotypes (the number of unique haplotypes), rather than their evenness (the extent of similarity in relative abundances). Taken together, this pattern supports a continuous emergence and extinction of the gene alleles adaptive to virulence sink habitats of E. coli, rather than a one-time change in the habitat conditions. Thus, ecological methods of species diversity analysis can be successfully adapted to characterize the emergence of microbial virulence in bacterial pathogens subject to source-sink dynamics.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Sujay
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Michael
authors.initials: M
authors.lastname: Feldgarden
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Weissman
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Dykhuizen
authors.forename: Gerald
authors.initials: G
authors.lastname: van Belle
authors.forename: Evgeni V
authors.initials: EV
authors.lastname: Sokurenko
mesh_terms: D018830:Adhesins, Escherichia coli / Q000235:genetics*; D004926:Escherichia coli / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics; D005243:Feces / Q000382:microbiology; D036781:Fimbriae Proteins / Q000235:genetics*; D014644:Genetic Variation; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D012641:Selection, Genetic; D014552:Urinary Tract Infections / Q000382:microbiology*
chemical_list: D018830:Adhesins, Escherichia coli; D029968:Escherichia coli Proteins; C058769:fimH protein, E coli; D036781:Fimbriae Proteins