From colonization to invasion: genomic and phenotypic comparison of faecal and bloodstream isolates from the same...

Area of Science:

• Microbiology
• Genomics
• Infectious Diseases

Background:

• Gram-negative bloodstream infections (GNBSI) are a major global health concern.
• Healthcare-associated GNBSI are frequently caused by Escherichia coli and Klebsiella pneumoniae, often originating from gastrointestinal tract (GIT) colonization.
• The precise mechanisms by which GIT colonization leads to invasive GNBSI remain incompletely understood.

Purpose of the Study:

• To investigate the genomic and phenotypic adaptations of E. coli and K. pneumoniae during the transition from GIT colonization to invasive bloodstream infection.
• To understand the within-host evolution of Gram-negative pathogens.

Main Methods:

• Comparative analysis of linked fecal and blood isolates from pediatric patients with healthcare-associated GNBSI.
• Whole-genome sequencing, comparative average nucleotide identity, and core genome single nucleotide polymorphism (SNP) analysis.
• Phenotypic assays for antimicrobial resistance and biofilm formation.

Main Results:

• Five highly related isolate pairs (three E. coli, two K. pneumoniae) confirmed the GIT origin of bloodstream infections.
• Isolates within pairs shared identical virulence genes, but exhibited changes in antimicrobial susceptibility.
• Four out of five isolate pairs showed increased biofilm formation, with one pair also displaying altered antimicrobial resistance gene profiles.

Conclusions:

• This study offers insights into the within-host evolutionary processes driving Gram-negative pathogen transition from GIT colonization to bloodstream invasion.
• Metabolic adaptation and biofilm formation appear to be convergent traits advantageous for healthcare-associated GNBSI.
• Further research with larger cohorts and functional validation of mutations is necessary to elucidate GNBSI pathogenesis.