Horizontal gene transfer linked to K. pneumoniae host adaptation
Gut colonization by the Gram-negative bacillus Klebsiella pneumoniae is a significant risk factor for extra-intestinal infections. However, the mechanisms by which this opportunistic pathogen causes disseminated infections remain poorly understood. To investigate this phenomenon, 22 strain pairs of Klebsiella spp. were sequentially isolated from rectal swabs and blood samples of ICU patients. All strains poorly adhered to intestinal epithelial cells in vitro, and failed to invade or disrupt epithelial barrier integrity. Few phenotypic differences between strains of the same pair were observed regarding their biofilm-forming capacities and antibiotics resistance. Whole genome sequencing of five pairs showed diverse sequence types, the presence of numerous antibiotics resistance genes but few virulence genes. Pairwise comparison of genomic sequences of blood and rectal isolates evidenced a few single nucleotide polymorphisms and small insertions-deletions, mostly affecting genes involved in biosynthesis of surface structures (such as capsules, pili). Most genetic changes were driven by horizontal gene transfer events, with the notable acquisition of a plasmid that enhanced bacterial fitness by eliminating competitors. In addition, some blood isolates had reduced the number of antibiotic resistance genes, underscoring the high plasticity of the Klebsiella resistome. Finally, one bloodstream isolate carried a mutS mutation, conferring a hypermutator phenotype that could increase evolvability despite the fitness burden. Together, these findings indicate that within-host genetic evolution, rather than the acquisition of virulence traits, can enhance the colonization, competitiveness and ultimately the ability of K. pneumoniae to cause invasive infections.
Gut colonization by the Gram-negative bacillus Klebsiella pneumoniae is a significant risk factor for extra-intestinal infections. However, the mechanisms by which this opportunistic pathogen causes disseminated infections remain poorly understood. To investigate this phenomenon, 22 strain pairs of Klebsiella spp. were sequentially isolated from rectal swabs and blood samples of ICU patients. All strains poorly adhered to intestinal epithelial cells in vitro, and failed to invade or disrupt epithelial barrier integrity. Few phenotypic differences between strains of the same pair were observed regarding their biofilm-forming capacities and antibiotics resistance. Whole genome sequencing of five pairs showed diverse sequence types, the presence of numerous antibiotics resistance genes but few virulence genes. Pairwise comparison of genomic sequences of blood and rectal isolates evidenced a few single nucleotide polymorphisms and small insertions-deletions, mostly affecting genes involved in biosynthesis of surface structures (such as capsules, pili). Most genetic changes were driven by horizontal gene transfer events, with the notable acquisition of a plasmid that enhanced bacterial fitness by eliminating competitors. In addition, some blood isolates had reduced the number of antibiotic resistance genes, underscoring the high plasticity of the Klebsiella resistome. Finally, one bloodstream isolate carried a mutS mutation, conferring a hypermutator phenotype that could increase evolvability despite the fitness burden. Together, these findings indicate that within-host genetic evolution, rather than the acquisition of virulence traits, can enhance the colonization, competitiveness and ultimately the ability of K. pneumoniae to cause invasive infections.
Universite Clermont Auvergne