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Cited by 1Antibiotic Resistance in BacteriaTuberculosis Research and EpidemiologyMicrobial Natural Products and Biosynthesis

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A macroevolution-inspired approach to reveal novel antibiotic resistance mechanisms

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Subtil, Fernanda T, Machado, Teresa FG, Douglas, Holly, Kirkpatrick, Joanna M, Skehel, Mark, Garza-Garcia, Acely, de Carvalho, Luiz Pedro S·2026·eLife
DOI 10.7554/elife.101940PMC PMC13246000

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Abstract

With the continuous rise in antibiotic resistance, novel methods that can reveal currently unknown antibiotic resistance mechanisms are essential to prepare and inform health responses and novel antibiotic discovery campaigns. Here, we built a library of species representative of the genus Mycobacterium and determined their antibiotic resistance profiles, allowing for the first time systematic multispecies comparisons. Analyzing antibiotic resistance in the context of other closely related yet diverse organisms revealed species with truly exceptional traits as well as general principles underpinning antibiotic resistance. Among these, we reveal that intrabacterial accumulation of antibiotics does not correlate with their potency at the species level. Our data also reveals that rifamycin resistance in mycobacteria is dominantly caused by antibiotic modification, contrary to what has been observed in Mycobacterium tuberculosis . Our data provides a solid starting point for the exploration of novel determinants of antibiotic resistance. We illustrate the utility of this species-level approach to discovery of novel traits by characterizing a previously unrecognized rifamycin-inactivating enzyme group that is present in a wide range of bacterial genera.

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Metadata

Authors
Subtil, F. T., Machado, T. F., Douglas, H., Kirkpatrick, J. M., Skehel, M., Garza-Garcia, A., & de Carvalho, L. P. S.
Affiliations
  • The Francis Crick Institute (GB)
  • Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute
Corresponding author
de Carvalho, Luiz Pedro S
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2026-06-08
Volume
13
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.101940
PMC
PMC13246000
OpenAlex
W4404240676
Cited by
1
References
1
Citations by year
2026: 1
Type
posted content
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • The Francis Crick Institute (FC001060)
  • Wellcome Trust (104785/B/14/Z)
Topics
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
Keywords
antibiotic resistance mechanisms, Mycobacterium, rifamycin resistance, antibiotic modification, macroevolution, new antibiotic development, Mycobacterium tuberculosis
MeSH terms
Anti-Bacterial Agents, Mycobacterium, Rifamycins, Evolution, Molecular, Drug Resistance, Bacterial

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