Pseudomonas aeruginosa Initiates a Rapid and Specific Transcriptional Response during Surface Attachment.

Pseudomonas aeruginosa Initiates a Rapid and Specific Transcriptional Response during Surface Attachment.
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DOI:
10.1128/jb.00086-22
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发表时间:
2022-05-17
影响因子:
3.2
通讯作者:
--
中科院分区:
生物学3区
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铜绿假单胞菌的慢性生物膜感染是导致患者发病和死亡的主要原因。多细胞细菌聚集体(称为生物膜)的形成与抗菌药物和免疫清除的抵抗力增强以及感染的持续存在有关。生物膜的形成依赖于细菌细胞对表面的附着,因此,附着在慢性感染中起着关键作用。我们假设细菌感知各种表面并启动快速、特定的反应以增加粘附并建立生物膜。 RNA 测序 (RNA-Seq) 分析确定了贴壁细胞在初始附着过程中的转录变化,从而确定了细菌在 1 小时内对非生物表面的反应。随后的筛选研究了表面附着中最受高度调控的基因,确定了 4 个基因:pfpI、phnA、leuD 和 moaE,所有这些基因在代谢和生物膜形成中都发挥作用。此外,还比较了初始附着后对几种不同的医学相关非生物表面的转录反应。令人惊讶的是,每个表面都有特定的转录反应,一般来说,很少有基因受到表面反应的调节。我们鉴定了一组 20 个基因,它们在所有三个表面上都有差异表达,其中许多具有代谢功能,包括钼蝶呤辅因子生物合成和氮代谢。这项研究增进了对细菌对表面转录反应的动力学和特异性的理解,并表明代谢线索是从浮游生活方式向生物膜生活方式转变过程中的重要信号。重要性细菌生物膜是生活许多方面的一个重要问题,包括气道、伤口和留置医疗器械的慢性感染;与食品生产相关的工业表面和海洋表面的生物污垢;和医院感染。了解表面粘附力可能会影响生活的许多领域。这项研究以一种新颖的方法利用新兴技术来解决细菌生物膜发育的关键步骤。这些发现阐明了对几种与疾病相关的非生物表面的保守反应和表面特异性反应。未来的工作将在本报告的基础上进行扩展,以确定生物膜的启动机制,目的是确定可预防生物膜的细菌因素。
Chronic biofilm infections by Pseudomonas aeruginosa are a major contributor to the morbidity and mortality of patients. The formation of multicellular bacterial aggregates, called biofilms, is associated with increased resistance to antimicrobials and immune clearance and the persistence of infections. Biofilm formation is dependent on bacterial cell attachment to surfaces, and therefore, attachment plays a key role in chronic infections. We hypothesized that bacteria sense various surfaces and initiate a rapid, specific response to increase adhesion and establish biofilms. RNA sequencing (RNA-Seq) analysis identified transcriptional changes of adherent cells during initial attachment, identifying the bacterial response to an abiotic surface over a 1-h period. Subsequent screens investigating the most highly regulated genes in surface attachment identified 4 genes, pfpI, phnA, leuD, and moaE, all of which have roles in both metabolism and biofilm formation. In addition, the transcriptional responses to several different medically relevant abiotic surfaces were compared after initial attachment. Surprisingly, there was a specific transcriptional response to each surface, with very few genes being regulated in response to surfaces in general. We identified a set of 20 genes that were differentially expressed across all three surfaces, many of which have metabolic functions, including molybdopterin cofactor biosynthesis and nitrogen metabolism. This study has advanced the understanding of the kinetics and specificity of bacterial transcriptional responses to surfaces and suggests that metabolic cues are important signals during the transition from a planktonic to a biofilm lifestyle. IMPORTANCE Bacterial biofilms are a significant concern in many aspects of life, including chronic infections of airways, wounds, and indwelling medical devices; biofouling of industrial surfaces relevant for food production and marine surfaces; and nosocomial infections. The effects of understanding surface adhesion could impact many areas of life. This study utilized emerging technology in a novel approach to address a key step in bacterial biofilm development. These findings have elucidated both conserved and surface-specific responses to several disease-relevant abiotic surfaces. Future work will expand on this report to identify mechanisms of biofilm initiation with the aim of identifying bacterial factors that could be targeted to prevent biofilms.
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