# Perillaldehyde combined with domiphen: synergistic bactericidal and anti-biofilm activity against Staphylococcus aureus and Escherichia coli

**Authors:** Jiaju Qiao, Shengmin Wu, Cuiyan Fu, Quanlin Zhao, Yang Gong, Linjie Xu, Dandan Tang, Yuan Gao, Wanyi Luo

PMC · DOI: 10.3389/fcimb.2026.1769865 · Frontiers in Cellular and Infection Microbiology · 2026-03-10

## TL;DR

A combination of perillaldehyde and domiphen effectively kills bacteria and disrupts biofilms, showing promise for controlling infections caused by Staphylococcus aureus and Escherichia coli.

## Contribution

The study introduces a synergistic combination of perillaldehyde and domiphen for combating bacterial biofilms.

## Key findings

- The combination showed a synergistic effect with a fractional inhibitory concentration index of less than 0.36.
- It reduced biofilm mass by over 53% and decreased viable bacterial counts by 103 CFU/mL.
- The treatment improved survival rates in Galleria mellonella larvae infected with the bacteria.

## Abstract

Biofilms formed by pathogenic bacteria such as Staphylococcus aureus and Escherichia coli pose a significant threat to public health. Combination therapy has emerged as a promising strategy to combat bacterial infections and biofilm formation. In this study, the natural product perillaldehyde and the surfactant domiphen were evaluated for their ability to inhibit biofilm formation by these pathogenic strains.

The antimicrobial activity of perillaldehyde and domiphen, alone and in combination, was assessed against S. aureus and E. coli strains. Synergism was determined by calculating the fractional inhibitory concentration index. Biofilm mass was evaluated using the crystal violet staining assay, and the viability of biofilm cells on stainless steel and polyethylene surfaces was examined via viable cell counting. Additionally, the therapeutic potential of the combination was further assessed using a Galleria mellonella larval infection model.

The combination of perillaldehyde and domiphen showed synergistic effects against both pathogenic strains, with a fractional inhibitory concentration index of less than 0.36. The combination of 1 μL/mL perillaldehyde and 1 μg/mL domiphen dispersed more than 53% of the biofilm mass in both S. aureus and E. coli strains. In addition, the combination reduced the total viable bacterial counts in biofilms on stainless steel and polyethylene surfaces by approximately 103 CFU/mL. The treatment also significantly improved the survival rate of G. mellonella larvae infected with the bacteria.

These results indicate that the novel combination of perillaldehyde and domiphen has the potential to decrease biofilm formation on various industrial material surfaces.

## Linked entities

- **Chemicals:** perillaldehyde (PubChem CID 16441), domiphen (PubChem CID 3149)
- **Species:** Staphylococcus aureus (taxon 1280), Escherichia coli (taxon 562), Galleria mellonella (taxon 7137)

## Full-text entities

- **Diseases:** bacterial infections (MESH:D001424), infection (MESH:D007239)
- **Chemicals:** polyethylene (MESH:D020959), crystal violet (MESH:D005840), domiphen (MESH:C007556), Perillaldehyde (MESH:C033342), stainless steel (MESH:D013193)
- **Species:** Staphylococcus aureus (species) [taxon 1280], Escherichia coli (E. coli, species) [taxon 562], Galleria mellonella (greater wax moth, species) [taxon 7137]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13008891/full.md

## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC13008891/full.md

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Source: https://tomesphere.com/paper/PMC13008891