奇异变形杆菌和粪肠球菌之间的代谢相互作用促进了多微生物生物膜的形成和侵袭性疾病的发生。

IF 5.1 1区 生物学 Q1 MICROBIOLOGY
mBio Pub Date : 2024-10-30 DOI:10.1128/mbio.02164-24
Benjamin C Hunt, Vitus Brix, Joseph Vath, Lauren Beryl Guterman, Steven M Taddei, Namrata Deka, Brian S Learman, Aimee L Brauer, Shichen Shen, Jun Qu, Chelsie E Armbruster
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引用次数: 0

摘要

生物膜在导尿管相关性尿路感染(CAUTI)的发生和致病过程中发挥着重要作用。mirabilis 变形杆菌和粪肠球菌是常见的 CAUTI 病原体,它们会持续共同定殖导尿管尿路并形成生物膜,生物量和抗生素耐药性都会增加。在本研究中,我们揭示了促使生物膜增强的代谢相互作用,并研究了其对 CAUTI 严重程度的影响。通过对生物膜的成分和蛋白质组分析,我们确定生物膜生物量的增加源于多微生物生物膜蛋白质部分的增加。我们进一步观察到,与单种生物膜相比,多微生物生物膜中与鸟氨酸和精氨酸代谢相关的蛋白质更为丰富。我们的研究表明,粪肠球菌的精氨酸/鸟氨酸反转运体促进了 mirabilis 中精氨酸的生物合成和代谢,最终推动了多微生物生物膜蛋白质含量的增加,而不会影响任何一种生物膜的存活率。我们进一步研究发现,破坏粪肠球菌鸟氨酸反转运口会改变多微生物生物膜的代谢轮廓,并阻止生物膜的增强,而补充外源性鸟氨酸可弥补这一缺陷。在小鼠 CAUTI 模型中,鸟氨酸转运体对粪肠球菌的定植没有作用,但对泌尿系结石形成和菌血症的发生率增加有作用,这种情况在奇异变形杆菌引起的多微生物 CAUTI 中会发生。因此,破坏常见共定植物种之间的新陈代谢相互作用可能是降低菌血症风险的可行策略。在导尿管泌尿道中,潜在的病原体会长期共同定殖,它们之间的相互作用会导致更严重的疾病后果。在这项研究中,我们发现代谢产物 L-鸟氨酸是粪肠球菌和奇异变形杆菌这两种常见且具有挑战性的病原体之间发生疾病增强作用的关键介质。因此,破坏鸟氨酸介导的相互作用可能是防止多微生物生物膜形成和降低严重疾病风险的一种策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metabolic interplay between Proteus mirabilis and Enterococcus faecalis facilitates polymicrobial biofilm formation and invasive disease.

Biofilms play an important role in the development and pathogenesis of catheter-associated urinary tract infection (CAUTI). Proteus mirabilis and Enterococcus faecalis are common CAUTI pathogens that persistently co-colonize the catheterized urinary tract and form biofilms with increased biomass and antibiotic resistance. In this study, we uncover the metabolic interplay that drives biofilm enhancement and examine the contribution to CAUTI severity. Through compositional and proteomic biofilm analyses, we determined that the increase in biofilm biomass stems from an increase in the protein fraction of the polymicrobial biofilm. We further observed an enrichment in proteins associated with ornithine and arginine metabolism in polymicrobial biofilms compared with single-species biofilms. We show that arginine/ornithine antiport by E. faecalis promotes arginine biosynthesis and metabolism in P. mirabilis, ultimately driving the increase in polymicrobial biofilm protein content without affecting viability of either species. We further show that disrupting E. faecalis ornithine antiport alters the metabolic profile of polymicrobial biofilms and prevents enhancement, and this defect was complemented by supplementation with exogenous ornithine. In a murine model of CAUTI, ornithine antiport did not contribute to E. faecalis colonization but was required for the increased incidence of urinary stone formation and bacteremia that occurs during polymicrobial CAUTI with P. mirabilis. Thus, disrupting metabolic interplay between common co-colonizing species may represent a viable strategy for reducing risk of bacteremia.IMPORTANCEChronic infections often involve the formation of antibiotic-resistant biofilm communities that include multiple different microbes, which pose a challenge for effective treatment. In the catheterized urinary tract, potential pathogens persistently co-colonize for long periods of time and the interactions between them can lead to more severe disease outcomes. In this study, we identified the metabolite L-ornithine as a key mediator of disease-enhancing interactions between two common and challenging pathogens, Enterococcus faecalis and Proteus mirabilis. Disrupting ornithine-mediated interactions may therefore represent a strategy to prevent polymicrobial biofilm formation and decrease risk of severe disease.

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来源期刊
mBio
mBio MICROBIOLOGY-
CiteScore
10.50
自引率
3.10%
发文量
762
审稿时长
1 months
期刊介绍: mBio® is ASM''s first broad-scope, online-only, open access journal. mBio offers streamlined review and publication of the best research in microbiology and allied fields.
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