Interplay of virulence factors shapes ecology and treatment outcomes in polymicrobial infections

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-09-06 DOI:10.1016/j.mbs.2024.109293

C. Herzberg , E.N. van Meegen , J.G.C. van Hasselt

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引用次数: 0

Abstract

Polymicrobial infections, caused by a community of multiple micro-organisms, are often associated with increased infection severity and poorer patient outcomes. The design of improved antimicrobial treatment strategies for PMIs can be supported by an understanding of their ecological and evolutionary dynamics. Bacterial species present in polymicrobial infections can produce virulence factors to inhibit host immune responses, such as neutrophil recruitment and phagocytosis. The presence of virulence factors can indirectly affect other bacterial species acting as a type of host-mediated interspecies interaction. The aim of this study was to assess how bacterial virulence factors targeting neutrophil function influence ecology and treatment outcomes of PMIs. An agent-based model was constructed which describes a dual-species bacterial population in the presence of neutrophils and a bacteriostatic drug. Our analysis has revealed unforeseen dynamics of the interplay of multiple virulence factors acting as interspecies interaction. We found that the distribution of two phagocytosis-inhibiting virulence factors amongst species can impact whether they have a mutually protective effect for both species. The addition of a virulence factor inhibiting neutrophil recruitment was found to reduce the protective effect of phagocytosis-inhibiting virulence factors. Furthermore we demonstrate the importance of virulence strength of a species relative to other virulent species to determine the fate of a species. We conclude that virulence factors are an important driver of population dynamics in polymicrobial infections, and may be a relevant therapeutic target for treatment of polymicrobial infections.

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毒力因素的相互作用影响着多微生物感染的生态学和治疗效果。

由多种微生物群落引起的多微生物感染往往与感染严重程度增加和患者预后较差有关。了解多微生物感染的生态和进化动态，有助于针对多微生物感染设计更好的抗菌治疗策略。存在于多微生物感染中的细菌可产生毒力因子来抑制宿主的免疫反应，如中性粒细胞的招募和吞噬作用。毒力因子的存在会间接影响其他细菌物种，这也是一种宿主介导的种间相互作用。本研究旨在评估针对中性粒细胞功能的细菌毒力因子如何影响 PMIs 的生态学和治疗效果。我们构建了一个基于代理的模型，该模型描述了存在中性粒细胞和抑菌药物的双种细菌种群。我们的分析揭示了作为种间相互作用的多种毒力因子相互作用的未预见动态。我们发现，两种抑制吞噬作用的毒力因子在物种间的分布会影响它们是否对两个物种都有相互保护的作用。我们发现，添加抑制中性粒细胞募集的毒力因子会降低吞噬抑制毒力因子的保护作用。此外，我们还证明了一个物种的毒力强度相对于其他毒力物种的重要性，这决定了一个物种的命运。我们的结论是，毒力因子是多微生物感染中种群动态的重要驱动因素，可能是治疗多微生物感染的相关治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.