Burkholderia cepacia complex (Bcc) bacteria are intrinsically antimicrobial-resistant opportunistic pathogens and key risk species in the contamination of nonfood industrial products. New agents and formulations to prevent growth of Burkholderia in home care (cleaning agents) and personal-care (cosmetics and toiletries) products are required. We characterized how ethylzingerone [4-(3-ethoxy-4-hydroxyphenyl) butan-2-one] (HEPB) acts as a preservative with activity against Burkholderia species encountered in industry. Burkholderia (n = 58) and non-Burkholderia (n = 7) bacteria were screened for susceptibility to HEPB, and its mode of action and resistance were determined for a model Burkholderia vietnamiensis strain using transposon mutagenesis, transcriptomics, and genome resequencing analysis. The susceptibility of Burkholderia spp. to HEPB (MIC = 0.45% ± 0.11% [wt/vol]; MBC = 0.90% ± 0.3% [wt/vol]) was characterized, with limited inter- and intraspecies differences. HEPB (1% [wt/vol]) was rapidly bactericidal, producing a 6-log reduction in viability within 4 h. Spontaneous resistance to HEPB did not develop, but transient phenotypes with altered growth characteristics and susceptibility to antibiotics were identified after prolonged exposure to sublethal HEPB concentrations. Transposon mutagenesis and RNA-sequencing analysis identified multiple genetic pathways associated with HEPB exposure, including stress response mechanisms, altered permeability, regulation of intracellular pH, damage and repair of intracellular components, and alteration and repair of lipopolysaccharides. Key pathways included the stringent response, homeostasis of intracellular pH by the kdp operon, protection against electrophiles by KefC, and repair of oxidized proteins by methionine sulfoxide reductase enzymes. In summary, we show that HEPB has potent, targeted efficacy against Burkholderia bacteria without promoting wider stable antimicrobial resistance. The mode of action of HEPB against Burkholderia is multifactorial, but killing by intracellular oxidation is a key mechanism of this promising agent.

中文翻译：

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绘制 Ethylzingerone [4-(3-Ethoxy-4-Hydroxyphenyl) Butan-2-One] 作为抗伯克霍尔德菌的活性剂的功效和作用方式。

洋葱伯克霍尔德菌复合体 (Bcc) 细菌本质上是抗微生物的机会性病原体，是非食品工业产品污染的关键风险物种。需要新的试剂和配方来防止家庭护理（清洁剂）和个人护理（化妆品和盥洗用品）产品中伯克霍尔德氏菌的生长。我们描述了 ethylzingerone [4-(3-ethoxy-4-hydroxyphenyl) butan-2-one] (HEPB) 如何作为防腐剂对工业中遇到的伯克霍尔德菌属具有活性。伯克霍尔德菌( n = 58) 和非伯克霍尔德菌( n= 7) 筛选细菌对 HEPB 的敏感性，并使用转座子诱变、转录组学和基因组重测序分析确定越南伯克霍尔德菌模型菌株的作用方式和抗性。伯克霍尔德菌的易感性spp. 对 HEPB (MIC = 0.45% ± 0.11% [wt/vol]; MBC = 0.90% ± 0.3% [wt/vol]) 进行了表征，种间和种内差异有限。HEPB (1% [wt/vol]) 具有快速杀菌作用，在 4 小时内使活力降低 6 个对数。对 HEPB 的自发抗性没有发展，但在长期暴露于亚致死 HEPB 浓度后，鉴定出具有改变的生长特征和对抗生素敏感性的短暂表型。转座子诱变和 RNA 测序分析确定了与 HEPB 暴露相关的多种遗传途径，包括应激反应机制、改变的通透性、细胞内 pH 值的调节、细胞内成分的损伤和修复，以及脂多糖的改变和修复。关键途径包括严格反应、细胞内 pH 值的稳态kdp操纵子，KefC 保护亲电体，蛋氨酸亚砜还原酶修复氧化蛋白质。总之，我们表明 HEPB 对伯克霍尔德菌具有有效的靶向功效，而不会促进更广泛的稳定抗菌素耐药性。HEPB 对伯克霍尔德菌的作用方式是多因素的，但通过细胞内氧化杀死是这种有前途的药物的关键机制。