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Volume 171, Issue 6

History shapes regulatory and evolutionary responses to tigecycline in two reference strains of Open Access

Abstract

Evolutionary history encompasses both genetic and phenotypic bacterial differences; however, the extent to which this history influences drug response and antimicrobial resistance (AMR) adaptation remains unclear. Historical contingencies arise when elements from an organism’s past leave lasting effects on the genome, altering the paths available for adaptation. Here, we compare two diverging reference strains of , representative of archaic and contemporary infections, to study the impact of deep historical differences shaped by decades of adaptation in varying antibiotic and host pressures. We evaluated these effects by comparing immediate and adaptive responses to the last-resort antibiotic, tigecycline (TGC). The strains demonstrated divergent transcriptional responses, suggesting that baseline transcript levels may dictate global responses to antibiotics. Experimental evolution in TGC revealed clear differences in population dynamics, with hard sweeps in populations founded by one strain and no mutations reaching fixation in the other strain. AMR was acquired through predictable mechanisms of increased efflux and drug target modification; however, efflux targets were dictated by strain background. Genetic adaptation may outweigh historic differences in transcriptional networks, as evolved populations no longer show transcriptomic signatures of drug response. Importantly, fitness–resistance trade-offs were only observed in lineages evolved from the archaic strain, while the contemporary reference isolate suffered no fitness defects. This suggests that decades of adaptation to antibiotics resulted in pre-existing compensatory mechanisms in the more contemporary isolate, an important example of a beneficial effect of historical contingencies.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antimicrobial resistance , evolutionary history , experimental evolution , transcriptomics and Acinetobacter baumannii
Funding
This study was supported by the:
  • Ministerio de Ciencia, Innovación y Universidades (Award RYC2022-037765-I)
    • Principle Award Recipient: AlfonsoSantos Lopez
  • Pennsylvania Department of Health (Award CURES 4100085725)
    • Principle Award Recipient: VaughnCooper
  • National Institute of Allergy and Infectious Diseases (Award F31AI172279)
    • Principle Award Recipient: AleciaB Rokes
  • National Institute of Allergy and Infectious Diseases (Award U19AI158076)
    • Principle Award Recipient: VaughnCooper
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2025-06-09
2025-07-08
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History shapes regulatory and evolutionary responses to tigecycline in two reference strains of Acinetobacter baumannii
Microbiology 171, 001570 (2025); https://doi.org/10.1099/mic.0.001570
/content/journal/micro/10.1099/mic.0.001570
/content/journal/micro/10.1099/mic.0.001570
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