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FabR,一种调节膜脂动态平衡的调节剂,参与生物膜的坚固性。

FabR, a regulator of membrane lipid homeostasis, is involved in biofilm robustness.

机构信息

Université Clermont Auvergne, CNRS, LMGE, Clermont-Ferrand, France.

Université Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.

出版信息

mBio. 2024 Oct 16;15(10):e0131724. doi: 10.1128/mbio.01317-24. Epub 2024 Sep 6.

DOI:10.1128/mbio.01317-24
PMID:39240091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11481535/
Abstract

Biofilm is a dynamic structure from which individual bacteria and micro-aggregates are released to subsequently colonize new niches by either detachment or dispersal. Screening of a transposon mutant library identified genes associated with the alteration of biofilm including , which encodes a transcriptional regulator involved in membrane lipid homeostasis. An isogenic ∆ mutant formed more biofilm than the wild-type (WT) strain and its trans-complemented strain. The thick and round aggregates observed with ∆ were resistant to extensive washes, unlike those of the WT strain. Confocal microscopy and BioFlux microfluidic observations showed that deletion was associated with biofilm robustness and impaired erosion over time. The genes and associated with fatty acid metabolism were significantly overexpressed in the ∆ strain, in both planktonic and biofilm conditions. Two monounsaturated fatty acids, palmitoleic acid (C16:1) and oleic acid (C18:1), were found in higher proportion in biofilm cells than in planktonic forms, whereas heptadecenoic acid (C17:1) and octadecanoic acid, 11-methoxy (C18:0-OCH3) were found in higher proportion in the planktonic lifestyle. The mutation induced variations in the fatty acid composition, with no clear differences in the amounts of saturated fatty acids (SFA) and unsaturated fatty acids for the planktonic lifestyle but lower SFA in the biofilm form. Atomic force microscopy showed that deletion of is associated with decreased cell rigidity in the biofilm lifestyle, as well as a softer, more elastic biofilm with increased cell cohesion compared to the wild-type strain.IMPORTANCE is an opportunistic pathogen responsible for a wide range of nosocomial infections. The success of this pathogen is due to its high resistance to antibiotics and its ability to form biofilms. The molecular mechanisms involved in biofilm formation have been largely described but the dispersal process that releases individual and aggregate cells from mature biofilm is less well documented while it is associated with the colonization of new environments and thus new threats. Using a multidisciplinary approach, we show that modifications of bacterial membrane fatty acid composition lead to variations in the biofilm robustness, and subsequent bacterial detachment and biofilm erosion over time. These results enhance our understanding of the genetic requirements for biofilm formation in that affect the time course of biofilm development and the embrittlement step preceding its dispersal that will make it possible to control infections.

摘要

生物膜是一种动态结构,其中个别细菌和微聚集体被释放出来,随后通过脱离或分散到新的小生境中进行定殖。转座子突变体文库的筛选鉴定了与生物膜改变相关的基因,包括编码参与膜脂质动态平衡的转录调节剂的 基因。与野生型(WT)菌株及其互补菌株相比,同基因 ∆突变体形成的生物膜更多。与 WT 菌株不同,观察到的 ∆形成的厚而圆的聚集体耐广泛洗涤。共聚焦显微镜和 BioFlux 微流控观察表明, 缺失与生物膜的坚固性和随时间推移的侵蚀受损有关。与脂肪酸代谢相关的基因 和 在 ∆ 菌株中显著过表达,无论是在浮游和生物膜条件下。两种单不饱和脂肪酸,棕榈油酸(C16:1)和油酸(C18:1)在生物膜细胞中的比例高于浮游形式,而十七碳烯酸(C17:1)和十八烷酸,11-甲氧基(C18:0-OCH3)在浮游生活方式中比例更高。 突变诱导脂肪酸组成的变化,浮游生活方式中饱和脂肪酸(SFA)和不饱和脂肪酸的量没有明显差异,但生物膜形式中的 SFA 较低。原子力显微镜显示, 缺失与生物膜生活方式中 细胞刚性降低有关,与野生型菌株相比,生物膜更软、更有弹性,细胞间凝聚力增加。

意义

是一种机会性病原体,可引起广泛的医院获得性感染。这种病原体的成功归因于其对抗生素的高抗性及其形成生物膜的能力。生物膜形成涉及的分子机制已被广泛描述,但释放成熟生物膜中单个和聚集体细胞的分散过程记录较少,而该过程与新环境的定殖有关,因此会带来新的威胁。使用多学科方法,我们表明细菌膜脂肪酸组成的改变导致生物膜坚固性的变化,以及随后的细菌脱离和生物膜侵蚀随时间的推移。这些结果增强了我们对 生物膜形成的遗传要求的理解,这会影响生物膜发育的时间过程和其分散之前的变脆步骤,这将使其有可能控制 感染。

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