title: A phyletically rare gene promotes the niche-specific fitness of an E. coli pathogen during bacteremia.
abstract: In bacteria, laterally acquired genes are often concentrated within chromosomal regions known as genomic islands. Using a recently developed zebrafish infection model, we set out to identify unique factors encoded within genomic islands that contribute to the fitness and virulence of a reference urosepsis isolate-extraintestinal pathogenic Escherichia coli strain CFT073. By screening a series of deletion mutants, we discovered a previously uncharacterized gene, neaT, that is conditionally required by the pathogen during systemic infections. In vitro assays indicate that neaT can limit bacterial interactions with host phagocytes and alter the aggregative properties of CFT073. The neaT gene is localized within an integrated P2-like bacteriophage in CFT073, but was rarely found within other proteobacterial genomes. Sequence-based analyses revealed that neaT homologues are present, but discordantly conserved, within a phyletically diverse set of bacterial species. In CFT073, neaT appears to be unameliorated, having an exceptionally A+T-rich composition along with a notably altered codon bias. These data suggest that neaT was recently brought into the proteobacterial pan-genome from an extra-phyletic source. Interestingly, even in G+C-poor genomes, as found within the Firmicutes lineage, neaT-like genes are often unameliorated. Sequence-level features of neaT homologues challenge the common supposition that the A+T-rich nature of many recently acquired genes reflects the nucleotide composition of their genomes of origin. In total, these findings highlight the complexity of the evolutionary forces that can affect the acquisition, utilization, and assimilation of rare genes that promote the niche-dependent fitness and virulence of a bacterial pathogen.
authors: Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors: Travis J
authors: TJ
authors: Wiles
authors: J Paul
authors: JP
authors: Norton
authors: Sara N
authors: SN
authors: Smith
authors: Adam J
authors: AJ
authors: Lewis
authors: Harry L T
authors: HL
authors: Mobley
authors: Sherwood R
authors: SR
authors: Casjens
authors: Matthew A
authors: MA
authors: Mulvey
mesh_terms: D000818:Animals; D005075:Biological Evolution; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000382:microbiology; D004927:Escherichia coli Infections / Q000235:genetics / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000502:physiology*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D056084:Genetic Fitness; D016680:Genome, Bacterial; D044404:Genomic Islands; D054884:Host-Pathogen Interactions; D051379:Mice; D008808:Mice, Inbred CBA / Q000382:microbiology; D010802:Phylogeny; D014552:Urinary Tract Infections / Q000235:genetics / Q000382:microbiology*; D056689:Uropathogenic Escherichia coli / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics / Q000382:microbiology*
chemical_list: D029968:Escherichia coli Proteins