Evolutionary and functional history of the Escherichia coli K1 capsule

Abstract

Escherichia coli is a leading cause of invasive bacterial infections in humans. Capsule polysaccharide has an important role in bacterial pathogenesis, and the K1 capsule has been firmly established as one of the most potent capsule types in E. coli through its association with severe infections. However, little is known about its distribution, evolution and functions across the E. coli phylogeny, which is fundamental to elucidating its role in the expansion of successful lineages. Using systematic surveys of invasive E. coli isolates, we show that the K1-cps locus is present in a quarter of bloodstream infection isolates and has emerged in at least four different extraintestinal pathogenic E. coli (ExPEC) phylogroups independently in the last 500 years. Phenotypic assessment demonstrates that K1 capsule synthesis enhances E. coli survival in human serum independent of genetic background, and that therapeutic targeting of the K1 capsule re-sensitizes E. coli from distinct genetic backgrounds to human serum. Our study highlights that assessing the evolutionary and functional properties of bacterial virulence factors at population levels is important to better monitor and predict the emergence of virulent clones, and to also inform therapies and preventive medicine to effectively control bacterial infections whilst significantly lowering antibiotic usage.

A convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria

“…Compared to the capsule region of other ExPEC clones such as ST131, which has been significantly recombined 13 , 39 , the K1 capsule locus of ST95 strains is highly conserved and we found no evidence of recombination (Supplementary Fig. 1 ), a finding consistent with a recent study that examined a different ST95 strain collection 40 . In contrast, the genes encoding O antigen biosynthesis reside in a chromosomal recombination hotspot and their diversity reflects adaptation via host immune evasion 41 – 44 .…”

A live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections

“…3A ). However, the K1 capsule is known for its high resistance to the action of the complement 37 and other strains could be more or totally resistant if tested in this assay 38 , 39 . To confirm the specificity of the observed bactericidal activity, we tested other pathogenic Gram-negative bacteria ( Klebsiella pneumoniae and Pseudomonas aeruginosa PA14, previously used in killing experiments) as controls.…”

Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan

“…E. coli ST73 and ST95 represent two classical uropathogenic E. coli (UPEC) lineages that have been extensively studied experimentally in vitro and in vivo, and by using epidemiological surveys conducted both during the pre- and post-bacterial population genomics era 19 , 21 – 23 . A systematic comparison of the prevalence of these two lineages in neonatal colonisation with their prevalence in bacteremia surveillance indicated a heightened level of virulence but also wide circulation in the human population, as ST73 and ST95 were among the top four lineages identified in healthy babies 6 .…”