Genomic resistance in historical clinical isolates increased in frequency and mobility after the age of antibiotics

Antibiotic resistance is frequently observed shortly after the clinical introduction of an antibiotic. Whether and how frequently that resistance occurred before the introduction is harder to determine, as isolates could not have been tested for resistance before an antibiotic was discovered. Historical collections, like the British National Collection of Type Cultures (NCTC), stretching back to 1885, provide a window into this history. Here, we match 1,817 sequenced high-quality genomes from the NCTC collection to their respective year of isolation to study resistance genes before and concurrent with the age of antibiotics. Concordant with previous work, we find resistance genes in both pathogens and environmental samples before the age of antibiotics. While generally rare before the introduction of an antibiotic, we find an associated increase in frequency with antibiotic introduction. Finally, we observe a trend of resistance elements becoming both increasingly mobile and nested within multiple mobile elements as time goes on. More broadly, our findings suggest that likely functional antibiotic resistance genes were circulating in clinically relevant isolates before the age of antibiotics, but human usage is associated with increasing both their overall prevalence and mobility.