新出现的人类病原体 Photorhabdus asymbiotica 的温度诱导代谢转变。

IF 5 2区 生物学 Q1 MICROBIOLOGY mSystems Pub Date : 2024-11-19 Epub Date: 2024-10-24 DOI:10.1128/msystems.00970-23
Elena Lucy Carter, Nicholas R Waterfield, Chrystala Constantinidou, Mohammad Tauqeer Alam
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引用次数: 0

摘要

光habdus 是一种细菌属,包含昆虫病原体和新出现的人类病原体。大多数受昆虫限制的物种显示出温度限制,无法在 34°C 以上的温度下生长,而光照杆菌(Photorhabdus asymbiotica)可以在 37°C 的温度下生长,感染哺乳动物宿主并引起光照病。有人提出新陈代谢适应性有助于这种病原体在较高温度下生存,但人们对这些适应性背后的生物机制知之甚少。我们重建了一个经过大量人工编辑的 P. asymbiotica 基因组尺度代谢模型(iEC1073,BioModels ID MODEL2309110001),并通过硅基因敲除和营养物质利用实验进行了验证,实验数据与模型预测结果非常吻合。将 iEC1073 与 P. asymbiotica 在 28°C 和 37°C 温度条件下获得的转录组学数据相结合,可以建立温度特异性重构,代表病原体在哺乳动物宿主中转移到比昆虫宿主更高的温度时所经历的代谢适应性。对这些温度特异性重建的分析表明,核苷酸代谢富含预测的上调和下调反应:重要意义:光habdus 细菌物种中既有人类病原体,也有昆虫病原体,其中大多数物种无法在较高温度下生长。然而,同时感染人类和昆虫的Photorhabdus asymbiotica却能在较高温度下生长,并在37°C的温度下与昆虫体温相比发生新陈代谢适应性变化。因此,研究这种细菌如何进行新陈代谢适应以在更高温度下生存非常重要。在这项工作中,我们利用数学模型研究了细菌从 28°C 生长条件转换到 37°C 生长条件时发生的代谢转变。我们发现,P. asymbiotica 在 37 摄氏度时可能会出现预测的温度诱导代谢适应性变化,这种变化主要集中在核苷酸代谢途径中。
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A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbiotica.

Photorhabdus is a bacterial genus containing both insect and emerging human pathogens. Most insect-restricted species display temperature restriction, unable to grow above 34°C, while Photorhabdus asymbiotica can grow at 37°C to infect mammalian hosts and cause Photorhabdosis. Metabolic adaptations have been proposed to facilitate the survival of this pathogen at higher temperatures, yet the biological mechanisms underlying these are poorly understood. We have reconstructed an extensively manually curated genome-scale metabolic model of P. asymbiotica (iEC1073, BioModels ID MODEL2309110001), validated through in silico gene knockout and nutrient utilization experiments with an excellent agreement between experimental data and model predictions. Integration of iEC1073 with transcriptomics data obtained for P. asymbiotica at temperatures of 28°C and 37°C allowed the development of temperature-specific reconstructions representing metabolic adaptations the pathogen undergoes when shifting to a higher temperature in a mammalian compared to insect host. Analysis of these temperature-specific reconstructions reveals that nucleotide metabolism is enriched with predicted upregulated and downregulated reactions. iEC1073 could be used as a powerful tool to study the metabolism of P. asymbiotica, in different genetic or environmental conditions.

Importance: Photorhabdus bacterial species contain both human and insect pathogens, and most of these species cannot grow in higher temperatures. However, Photorhabdus asymbiotica, which infects both humans and insects, can grow in higher temperatures and undergoes metabolic adaptations at a temperature of 37°C compared to that of insect body temperature. Therefore, it is important to examine how this bacterial species can metabolically adapt to survive in higher temperatures. In this work, using a mathematical model, we have examined the metabolic shift that takes place when the bacteria switch from growth conditions in 28°C to 37°C. We show that P. asymbiotica potentially experiences predicted temperature-induced metabolic adaptations at 37°C predominantly clustered within the nucleotide metabolism pathway.

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来源期刊
mSystems
mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
10.50
自引率
3.10%
发文量
308
审稿时长
13 weeks
期刊介绍: mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.
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