Selection Footprint in the FimH Adhesin Shows Pathoadaptive Niche Differentiation in Escherichia coli

Abstract

Spread of biological species from primary into novel habitats leads to within-species adaptive niche differentiation and is commonly driven by acquisition of point mutations in individual genes that increase fitness in the alternative environment. However, finding footprints of adaptive niche differentiation in specific genes remains a challenge. Here we describe a novel method to analyze the footprint of pathogenicity-adaptive, or pathoadaptive, mutations in the Escherichia coli gene encoding FimH-the major, mannose-sensitive adhesin. Analysis of distribution of mutations across the nodes and branches of the FimH phylogenetic network shows (1) zonal separation of evolutionary primary structural variants of FimH and recently derived ones, (2) dramatic differences in the ratio of synonymous and nonsynonymous changes between nodes from different zones, (3) evidence for replacement hot-spots in the FimH protein, (4) differential zonal distribution of FimH variants from commensal and uropathogenic E. coli, and (5) pathoadaptive functional changes in FimH brought by the mutations. The selective footprint in fimH indicates that the pathoadaptive niche differentiation of E. coli is either in its initial stages or undergoing an evolutionary "source/sink" dynamic.

Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding

“…These strains are biased toward cystitis isolates because cystitis is significantly more common than pyelonephritis. FimC, the dedicated chaperone that mediates the assembly of FimH into type 1 pili (33), is not believed to be under positive selection (34,35) and thus served as a negative control. Maximum likelihood DNA phylograms were inferred using the fimH and fimC sequences from these 279 strains ( Fig.…”

Adaptive mutations in the signal peptide of the type 1 fimbrial adhesin of uropathogenic Escherichia coli

“…Indeed, fimH alleles with SP mutations appear to circulate only for a short time from an evolutionary perspective, as they do not accumulate silent changes. In this respect, the mutant SP alleles are similar to mutant mature protein alleles that enhance FimH's ability to bind at low shear conditions and are also selected in uropathogenic E. coli (23,33). A tradeoff of mature protein mutations could be a reduced resistance to adhesion inhibition by salivary proteins in the course of oropharyngeal colonization as a part of the fecal-oral transmission of E. coli (16).…”

“…Nonsynonymous mutations also occur at position Ϫ10, where valine was converted to isoleucine (V-10I) and alanine (V-10A). These findings and a lack of synonymous (silent) changes in the fimH signal sequence indicate positive selection in the FimH SP (23 Decreased Transport Activity of the SP Mutants. Both mutated SP amino acid positions are located in the hydrophobic core region, which spans positions Ϫ5 to Ϫ13 as predicted by the SignalP hidden Markov model (24) (Fig.…”

Microbial Speciation

“…An appropriate microbial GWAS should account for the degree of recombination or clonality in the population of interest (Falush and Bowden 2006;Chen and Shapiro 2015). Especially, in highly clonal populations, associations should be based on a convergence criterion (Sokurenko 2004;Chattopadhyay et al 2013), in which phenotypes of interest are acquired independently in different lineages (Fig. 6).…”