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Evol Appl. 2019 Jan 28;12(5):878-887. doi: 10.1111/eva.12762. eCollection 2019 Jun.

Patterns of cross-resistance and collateral sensitivity between clinical antibiotics and natural antimicrobials.

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European Centre for Environment and Human Health University of Exeter Medical School Cornwall UK.
Institute of Microbiology and Infection University of Birmingham Birmingham UK.
Department of Biostatistics University of Oslo Oslo Norway.
Department of Mathematics and Statistics University of Helsinki Helsinki Finland.
The Milner Centre for Evolution, Department of Biology & Biochemistry University of Bath Bath UK.


Bacteria interact with a multitude of other organisms, many of which produce antimicrobials. Selection for resistance to these antimicrobials has the potential to result in resistance to clinical antibiotics when active compounds target the same bacterial pathways. The possibility of such cross-resistance between natural antimicrobials and antibiotics has to our knowledge received very little attention. The antimicrobial activity of extracts from seaweeds, known to be prolific producers of antimicrobials, is here tested against Staphylococcus aureus isolates with varied clinical antibiotic resistance profiles. An overall effect consistent with cross-resistance is demonstrated, with multidrug-resistant S. aureus strains being on average more resistant to seaweed extracts. This pattern could potentially indicate that evolution of resistance to antimicrobials in the natural environment could lead to resistance against clinical antibiotics. However, patterns of antimicrobial activity of individual seaweed extracts vary considerably and include collateral sensitivity, where increased resistance to a particular antibiotic is associated with decreased resistance to a particular seaweed extract. Our correlation-based methods allow the identification of antimicrobial extracts bearing most promise for downstream active compound identification and pharmacological testing.


Antimicrobials; Staphylococcus aureus; antibiotic resistance; collateral sensitivity; cross‐resistance; seaweeds

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