Rossignol Tristan, Znaidi Sadri, Chauvel Murielle, Wesgate Rebecca, Decourty Laurence, Menard-Szczebara Florence, Cupferman Sylvie, Dalko-Sciba Maria, Barnes Rosemary, Maillard Jean-Yves, Saveanu Cosmin, d'Enfert Christophe
Unité Biologie et Pathogénicité Fongiques, USC2019 INRA, Institut Pasteur, Paris, France.
Laboratoire de Microbiologie Moléculaire, Vaccinologie et Développement Biotechnologique, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis-Belvédère, Tunisia.
Antimicrob Agents Chemother. 2021 Mar 18;65(4). doi: 10.1128/AAC.02711-20.
Preservatives increase the shelf life of cosmetic products by preventing growth of contaminating microbes, including bacteria and fungi. In recent years, the Scientific Committee on Consumer Safety (SCCS) has recommended the ban or restricted use of a number of preservatives due to safety concerns. Here, we characterize the antifungal activity of ethylzingerone (hydroxyethoxyphenyl butanone [HEPB]), an SCCS-approved new preservative for use in rinse-off, oral care, and leave-on cosmetic products. We show that HEPB significantly inhibits growth of , , and , acting fungicidally against Using transcript profiling experiments, we found that the transcriptome responded to HEPB exposure by increasing the expression of genes involved in amino acid biosynthesis while activating pathways involved in chemical detoxification/oxidative stress response. Comparative analyses revealed that phenotypic and transcriptomic responses to HEPB treatment were distinguishable from those of two widely used preservatives, triclosan and methylparaben. Chemogenomic analyses, using a barcoded nonessential mutant library, revealed that HEPB antifungal activity strongly interfered with the biosynthesis of aromatic amino acids. The Δ mutants in and were particularly sensitive to HEPB treatment, a phenotype rescued by exogenous addition of tryptophan to the growth medium, providing a direct link between HEPB mode of action and tryptophan availability. Collectively, our study sheds light on the antifungal activity of HEPB, a new molecule with safe properties for use as a preservative in the cosmetic industry, and exemplifies the powerful use of functional genomics to illuminate the mode of action of antimicrobial agents.
防腐剂通过防止包括细菌和真菌在内的污染微生物生长来延长化妆品的保质期。近年来，由于安全问题，消费者安全科学委员会（SCCS）已建议禁止或限制使用多种防腐剂。在此，我们对乙基姜酮（羟基乙氧基苯基丁酮[HEPB]）的抗真菌活性进行了表征，HEPB是一种经SCCS批准的新型防腐剂，可用于冲洗型、口腔护理和驻留型化妆品。我们发现HEPB能显著抑制白色念珠菌、近平滑念珠菌和热带念珠菌的生长，对白色念珠菌具有杀真菌作用。通过转录谱分析实验，我们发现白色念珠菌转录组对HEPB暴露的反应是增加参与氨基酸生物合成的基因表达，同时激活参与化学解毒/氧化应激反应的途径。比较分析表明，白色念珠菌对HEPB处理的表型和转录组反应与两种广泛使用的防腐剂三氯生和对羟基苯甲酸甲酯的反应不同。使用条形码化的白色念珠菌非必需突变体文库进行的化学基因组分析表明，HEPB的抗真菌活性强烈干扰芳香族氨基酸的生物合成。白色念珠菌和热带念珠菌中的Δ突变体对HEPB处理特别敏感，通过向生长培养基中外源添加色氨酸可挽救该表型，这直接将HEPB的作用模式与色氨酸可用性联系起来。总的来说，我们的研究揭示了HEPB的抗真菌活性，HEPB是一种具有安全特性的新分子，可在化妆品行业用作防腐剂，并且例证了功能基因组学在阐明抗菌剂作用模式方面的强大应用。
