Evolution of biofilm-adapted gene expression profiles in lasR-deficient clinical Pseudomonas aeruginosa isolates.

Evolution of biofilm-adapted gene expression profiles in lasR-deficient clinical Pseudomonas aeruginosa isolates.
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DOI:
10.1038/s41522-022-00268-1
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发表时间:
2022-02-14
影响因子:
9.2
通讯作者:
Häussler S
Häussler S
中科院分区:
生物学1区
文献类型:
--
作者:
Jeske A;Arce-Rodriguez A;Thöming JG;Tomasch J;Häussler S

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病原微生物的总体成功取决于其有效适应人类宿主中具有挑战性条件的能力。长期进化实验跟踪和预测适应性轨迹,并为我们理解细菌适应的驱动力做出了重大贡献。在这项研究中,我们进行了横截面研究,而不是长期的纵向进化实验。我们分析了大量临床铜绿假单胞菌分离株的转录谱以及基因组序列变异,这些分离株已从不同的感染人体部位回收。在不同的临床分离株组中发现了基因表达模式的趋同变化。大多数重复观察到的表达模式可以归因于一个有缺陷的lasR基因,该基因编码主要的群体感应调节器LasR。引人注目的是,lasR缺陷菌株的基因表达模式似乎反映了一种转录反应,该反应在与生物膜内生长一致的方向上演变。在遗传同化的过程中,lasR缺陷的铜绿假单胞菌分离株似乎组成型表达生物膜适应的转录谱,不再需要相应的环境触发。我们的研究结果表明,分析临床分离株中病理适应性突变的功能后果揭示了长期的进化途径,并可能解释在临床背景下机会致病菌铜绿假单胞菌中lasR突变体的成功。
The overall success of a pathogenic microbe depends on its ability to efficiently adapt to challenging conditions in the human host. Long-term evolution experiments track and predict adaptive trajectories and have contributed significantly to our understanding of the driving forces of bacterial adaptation. In this study, we conducted a cross-sectional study instead of long-term longitudinal evolution experiments. We analyzed the transcriptional profiles as well as genomic sequence variations of a large number of clinical Pseudomonas aeruginosa isolates that have been recovered from different infected human sites. Convergent changes in gene expression patterns were found in different groups of clinical isolates. The majority of repeatedly observed expression patterns could be attributed to a defective lasR gene, which encodes the major quorum-sensing regulator LasR. Strikingly, the gene expression pattern of the lasR-defective strains appeared to reflect a transcriptional response that evolves in a direction consistent with growth within a biofilm. In a process of genetic assimilation, lasR-deficient P. aeruginosa isolates appear to constitutively express a biofilm-adapted transcriptional profile and no longer require a respective environmental trigger. Our results demonstrate that profiling the functional consequences of pathoadaptive mutations in clinical isolates reveals long-term evolutionary pathways and may explain the success of lasR mutants in the opportunistic pathogen P. aeruginosa in a clinical context.
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