Defining Microbial Community Functions in Chronic Human Infection with Metatranscriptomics.

Defining Microbial Community Functions in Chronic Human Infection with Metatranscriptomics.
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用宏转录组学定义人类慢性感染中的微生物群落功能。

DOI:
10.1101/2023.06.06.543868
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发表时间:
2023
期刊:
bioRxiv : the preprint server for biology
影响因子:
--
通讯作者:
Ibberson,CarolynB
Ibberson,CarolynB
中科院分区:
--
文献类型:
--
作者:
Adekoya,AanuoluwaE;Kargbo,HoodyA;Ibberson,CarolynB

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慢性多种微生物感染(cPMI)包含具有不同代谢能力的复杂细菌群落,导致竞争和合作相互作用。尽管 cPMI 中存在的微生物是通过培养依赖性和非培养方法建立的,但驱动不同 cPMI 的关键功能以及这些复杂群落的代谢活动仍然未知。为了解决这一知识差距,我们分析了从囊性纤维化 (CF) 痰和慢性伤口感染 (CW) 中收集的 102 个已发表的宏转录组,以确定 cPMI 中的关键细菌成员和功能。群落组成分析发现病原体(特别是葡萄球菌和假单胞菌)以及微生物群的厌氧成员(包括卟啉单胞菌、厌氧球菌和普雷沃菌)的患病率很高。 HUMANn3 和 SAMSA2 的功能分析显示,虽然涉及细菌竞争、氧化应激反应和毒力的功能在两种慢性感染类型中都是保守的,但超过 40% 的功能表达存在差异。 CF 样品中抗生素耐药性和生物膜功能的表达较高,而 CW 样品中组织破坏酶和氧化应激反应功能的表达较高。值得注意的是,在 CW 和 CF 样本中,严格厌氧菌与传统病原体呈负相关,并且它们对这些功能的表达做出了显着贡献。此外,我们发现微生物群落具有独特的表达模式,并且不同的生物体在每个位点履行关键功能的表达,这表明感染环境强烈影响细菌的生理学,而群落结构影响功能。总的来说,我们的研究结果表明,群落组成和功能应该指导 cPMI 的治疗策略。 重要性 多种微生物感染 (PMI) 中的微生物多样性允许群落成员之间建立相互作用,这可能导致疾病结果增强,例如抗生素耐受性增加和慢性化。慢性 PMI 给卫生系统带来巨大负担,因为它们影响很大一部分人口,而且治疗费用昂贵且困难。然而,缺乏对实际人类感染部位微生物群落生理学的研究。在这里,我们强调,慢性 PMI 的主要功能不同,厌氧菌(通常被描述为旁观者)可能在慢性感染的进展中发挥重要作用。确定 PMI 中的群落结构和功能是了解增加这些环境中微生物群落毒力潜力的分子机制的关键一步。
Chronic polymicrobial infections (cPMIs) harbor complex bacterial communities with diverse metabolic capacities, leading to competitive and cooperative interactions. Although the microbes present in cPMIs have been established through culture-dependent and culture-independent methods, the key functions that drive different cPMIs and the metabolic activities of these complex communities remain unknown. To address this knowledge gap, we analyzed 102 published metatranscriptomes collected from cystic fibrosis (CF) sputum and chronic wound infections (CW) to identify key bacterial members and functions in cPMIs. Community composition analysis identified a high prevalence of pathogens, particularlyStaphylococcusandPseudomonas, and anaerobic members of the microbiota, includingPorphyromonas,Anaerococcus, andPrevotella. Functional profiling with HUMANn3 and SAMSA2 revealed that while functions involved in bacterial competition, oxidative stress response, and virulence were conserved across both chronic infection types, >40% of the functions were differentially expressed. Higher expression of antibiotic resistance and biofilm functions was observed in CF, while tissue-destructive enzymes and oxidative stress response functions were highly expressed in CW samples. Of note, strict anaerobes had negative correlations with traditional pathogens in both CW and CF samples, and they significantly contributed to the expression of these functions. Additionally, we show that microbial communities have unique expression patterns, and distinct organisms fulfill the expression of key functions in each site, indicating that the infection environment strongly influences bacterial physiology and that community structure influences function. Collectively, our findings indicate that community composition and function should guide treatment strategies for cPMIs.IMPORTANCEThe microbial diversity in polymicrobial infections (PMIs) allows for community members to establish interactions with one another, which can result in enhanced disease outcomes such as increased antibiotic tolerance and chronicity. Chronic PMIs result in large burdens on health systems, as they affect a significant proportion of the population and are expensive and difficult to treat. However, investigations into physiology of microbial communities in actual human infection sites are lacking. Here, we highlight that the predominant functions in chronic PMIs differ, and anaerobes, often described as bystanders, may be significant in the progression of chronic infections. Determining the community structure and functions in PMIs is a critical step toward understanding the molecular mechanisms that increase the virulence potential of the microbial community in these environments.
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