Genomic insights into preantibiotic osteomyelitis pathogens and their link to current resistant hospital strains

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OBJECTIVES: Osteomyelitis is a severe bone infection that was frequently fatal before the introduction of antibiotics and remains a significant healthcare burden today. Staphylococcus aureus is the most common cause, alongside other hospital-acquired pathogens. Despite their clinical importance, the evolutionary history of these bacteria remains poorly understood. We investigated historical osteomyelitis specimens to identify causative pathogens and characterise their genomes, virulence and antimicrobial resistance (AMR). METHODS: Seven osteomyelitis-affected bones from adults dating to 19th-20th century Germany were analysed using ancient DNA (aDNA) approaches. After sequencing and screening, candidate pathogens were prioritised based on authentic aDNA damage patterns, established association with osteomyelitis and exclusion as environmental contaminants. Identified species were characterised by phylogenetics, multilocus sequence typing and virulence/AMR profiling. RESULTS: In four patients, we detected authentic aDNA from Acinetobacter baumannii, S. aureus or Streptococcus pyogenes. Detected taxa in the remaining three patients did not fulfil the criteria for further analysis. Two patients carried A. baumannii genomes clustering closely with modern avian and freshwater isolates. Both harboured virulence genes, alongside intrinsic efflux pumps and β-lactamases. One patient carried an S. aureus strain belonging to the globally disseminated clonal complex 30, responsible for outbreaks since the 1950s. Molecular dating indicated that this strain diverged from the wider lineage around 1800, placing it among the earliest members of this group. It encoded multiple virulence genes, but no methicillin resistance genes. The fourth patient carried an S. pyogenes strain related to modern epidemic lineages from North America, encoding conserved virulence factors, but no AMR genes. CONCLUSIONS: These specimens provide a window into the evolution of osteomyelitis pathogens. Although modern developments such as widespread antibiotic use have intensified the global resistance crisis, our findings indicate that the genetic foundations for pathogenicity and resistance were already present more than 100 years ago.

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