Fungal control methods commonly involve the use of antifungals or preservatives, which can raise concerns about broader effects of these stressors on non-target organisms, spread of resistance and regulatory hurdles. Consequently, control methods enabling lower usage of such stressors are highly sought, for example chemical combinations that synergistically inhibit target-organisms. Here, we investigated how well such a principle extends to improving efficacy of an existing but tightly controlled food preservative, sorbic acid. A screen of ∼200 natural products for synergistic fungal inhibition in combinations with sorbic acid, in either 2% or 0.1% (w/v) glucose to simulate high or reduced-sugar foods, did not reveal reproducible synergies in either of the spoilage yeast species Saccharomyces cerevisiae or Zygosaccharomyces bailii. Potentially promising screen candidates (e.g. lactone parthenolide, ethyl maltol) or a small additional panel of rationally-selected compounds (e.g. benzoic acid) all gave Fractional Inhibitory Concentration Indices (FICI) ≥ 0.5 in combinations with sorbic acid, corroborating absence of synergy in either glucose condition (although FICI values did differ between the glucose conditions). Synergies were not achieved either in a tripartite combination with screen candidates or in a soft-drink formulation as matrix. In previous work with other stressors synergy 'hits' have been comparatively frequent, suggesting that sorbic acid could be unusually resistant to forming synergies with other potential inhibitors and this may relate to the weak acid's known multifactorial inhibitory-actions on cells. The study highlights a challenge in developing appropriate natural product or other chemical combinations applicable to food and beverage preservation.
Keywords: Checkerboard assay; Combinatorial synergy; Food spoilage; High throughput screen; Weak acid preservatives.
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