Understanding Stimulation of Conjugal Gene Transfer by Nonantibiotic Compounds: How Far Are We?

Zhiming He*, Arnaud Dechesne, Frank Schreiber, Yong-Guan Zhu, D. G. Joakim Larsson, Barth F. Smets*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


A myriad of nonantibiotic compounds is released into the environment, some of which may contribute to the dissemination of antimicrobial resistance by stimulating conjugation. Here, we analyzed a collection of studies to (i) identify patterns of transfer stimulation across groups and concentrations of chemicals, (ii) evaluate the strength of evidence for the proposed mechanisms behind conjugal stimulation, and (iii) examine the plausibility of alternative mechanisms. We show that stimulatory nonantibiotic compounds act at concentrations from 1/1000 to 1/10 of the minimal inhibitory concentration for the donor strain but that stimulation is always modest (less than 8-fold). The main proposed mechanisms for stimulation via the reactive oxygen species/SOS cascade and/or an increase in cell membrane permeability are not unequivocally supported by the literature. However, we identify the reactive oxygen species/SOS cascade as the most likely mechanism. This remains to be confirmed by firm molecular evidence. Such evidence and more standardized and high-throughput conjugation assays are needed to create technologies and solutions to limit the stimulation of conjugal gene transfer and contribute to mitigating global antibiotic resistance.
Original languageEnglish
JournalEnvironmental Science and Technology
Issue number21
Pages (from-to)9017-9030
Number of pages14
Publication statusPublished - 2024


  • Antibiotic resistance
  • Horizontal gene transfer
  • Conjugation
  • Reactive oxygen species
  • SOS response
  • Cell membrane permeability
  • Subinhibitory concentration
  • Chemicals


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