Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, United States.
J Nat Prod. 2024 Jun 28;87(6):1635-1642. doi: 10.1021/acs.jnatprod.4c00376. Epub 2024 May 30.
Biofilms commonly develop in immunocompromised patients, which leads to persistent infections that are difficult to treat. In the biofilm state, bacteria are protected against both antibiotics and the host's immune system; currently, there are no therapeutics that target biofilms. In this study, we screened a chemical fraction library representing the natural product capacity of the microbiota of marine egg masses, namely, the moon snail egg collars. This led to the identification of active fractions targeting both and biofilms. Subsequent analysis revealed that a subset of these fractions were capable of eradicating preformed biofilms, all against . Bioassay-guided isolation led us to identify pseudochelin A, a known siderophore, as a biofilm inhibitor with an IC of 88.5 μM. Mass spectrometry-based metabolomic analyses revealed widespread production of pseudochelin A among fractions possessing antibiofilm properties. In addition, a key biosynthetic gene involved in producing pseudochelin A was detected on 30% of the moon snail egg collars and pseudochelin A is capable of inhibiting the formation of biofilms (IC 50.6 μM) produced by ecologically relevant bacterial strains. We propose that pseudochelin A may have a role in shaping the microbiome or protecting the egg collars from microbiofouling.
生物膜通常在免疫功能低下的患者中形成,导致难以治疗的持续性感染。在生物膜状态下,细菌既能抵御抗生素,也能抵御宿主的免疫系统;目前,尚无针对生物膜的治疗方法。在这项研究中,我们筛选了一个代表海洋卵块(即月亮蜗牛卵环)微生物区系天然产物能力的化学部分文库,发现了针对 和 生物膜的活性部分。随后的分析表明,这些部分中的一部分能够消除已形成的生物膜,全部针对 。基于生物测定的分离使我们鉴定出了假霉素 A,一种已知的铁载体,它是一种 生物膜抑制剂,IC 为 88.5 μM。基于质谱的代谢组学分析表明,在具有 抗生物膜特性的部分中广泛产生了假霉素 A。此外,在 30%的月亮蜗牛卵环上检测到了参与产生假霉素 A 的关键生物合成基因,假霉素 A 能够抑制生态相关细菌菌株产生的生物膜形成(IC 50.6 μM)。我们提出,假霉素 A 可能在塑造微生物组或保护卵环免受微生物污染方面发挥作用。