Genome-informed metabolomic re-analysis identifies serum-associated amino acid signatures in sepsis-associated bacterial pathogens.

Background: Antibiotic-resistant bacterial infections remain a major global health threat, particularly in hospital settings. Standard antimicrobial susceptibility testing provides essential clinical information, but it does not fully capture pathogen metabolic adaptation under host-like conditions. Integrating isolate whole-genome sequencing with metabolomics may help prioritize condition-associated metabolic signatures linked to bacterial physiology and antibiotic response. Methods: We performed a secondary integrative re-analysis of publicly available isolate whole-genome sequencing and matched metabolomics datasets from Results: Metabolomic profiles showed condition-associated separation between RPMI and serum samples, with the most consistent serum-associated signature observed in Conclusion: This integrative re-analysis identified serum-associated amino acid remodeling as a prominent feature of host-like adaptation in Klebsiella. These findings provide candidate metabolic signatures for future mechanistic validation and suggest that serum exposure is associated with growth restriction and reduced antibiotic susceptibility under host-like conditions.