Department of Ecology, Evolution, and Environmental Biology, Columbia Universitygrid.21729.3f, New York, New York, USA.
Department of Epidemiology and Biostatistics, School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, New York, USA.
mSystems. 2022 Aug 30;7(4):e0048822. doi: 10.1128/msystems.00488-22. Epub 2022 Aug 8.
Host association-the selective adaptation of pathogens to specific host species-evolves through constant interactions between host and pathogens, leaving a lot yet to be discovered on immunological mechanisms and genomic determinants. The causative agents of Lyme disease (LD) are spirochete bacteria composed of multiple species of the Borrelia burgdorferi complex, including B. burgdorferi (), the main LD pathogen in North America-a useful model for the study of mechanisms underlying host-pathogen association. Host adaptation requires pathogens' ability to evade host immune responses, such as complement, the first-line innate immune defense mechanism. We tested the hypothesis that different host-adapted phenotypes among strains are linked to polymorphic loci that confer complement evasion traits in a host-specific manner. We first examined the survivability of 20 strains in sera and/or bloodstream and tissues from rodent and avian LD models. Three groups of complement-dependent host-association phenotypes emerged. We analyzed complement-evasion genes, identified among all strains and sequenced and compared genomes for individual strains representing each phenotype. The evolutionary history of loci is correlated with host-specific complement-evasion phenotypes, while comparative genomics suggests that several gene families and loci are potentially involved in host association. This multidisciplinary work provides novel insights into the functional evolution of host-adapted phenotypes, building a foundation for further investigation of the immunological and genomic determinants of host association. Host association is the phenotype that is commonly found in many pathogens that preferential survive in particular hosts. The Lyme disease (LD)-causing agent, B. burgdorferi (), is an ideal model to study host association, as is mainly maintained in nature through rodent and avian hosts. A widespread yet untested concept posits that host association in strains is linked to functional genetic variation conferring evasion to complement, an innate defense mechanism in vertebrate sera. Here, we tested this concept by grouping 20 strains into three complement-dependent host-association phenotypes based on their survivability in sera and/or bloodstream and distal tissues in rodent and avian LD models. Phylogenomic analysis of these strains further correlated several gene families and loci, including , with host-specific complement-evasion phenotypes. Such multifaceted studies thus pave the road to further identify the determinants of host association, providing mechanistic insights into host-pathogen interaction.
宿主关联——病原体对特定宿主物种的选择性适应——通过宿主和病原体之间的不断相互作用而进化，在免疫机制和基因组决定因素方面还有很多有待发现。莱姆病 (LD) 的病原体是由多种伯氏疏螺旋体组成的螺旋体细菌，包括伯氏疏螺旋体 (), 这是北美的主要 LD 病原体——是研究宿主-病原体关联机制的有用模型。宿主适应需要病原体逃避宿主免疫反应的能力，例如补体，这是一线先天免疫防御机制。我们测试了这样一个假设，即在不同宿主适应表型的菌株之间存在与多态性位点相关的假设，这些位点以宿主特异性的方式赋予补体逃避特性。我们首先检查了 20 株在来自啮齿动物和禽类 LD 模型的血清和/或血液以及组织中的存活率。出现了三组依赖补体的宿主关联表型。我们分析了补体逃避基因，在所有菌株中鉴定出 并对代表每种表型的单个菌株的基因组进行测序和比较。位点的进化历史与宿主特异性的补体逃避表型相关，而比较基因组学表明，几个基因家族和位点可能参与宿主关联。这项多学科工作为宿主适应表型的功能进化提供了新的见解，为进一步研究宿主关联的免疫和基因组决定因素奠定了基础。宿主关联是许多病原体中常见的表型，这些病原体更喜欢在特定宿主中生存。莱姆病 (LD) 病原体伯氏疏螺旋体 (), 是研究宿主关联的理想模型，因为 在自然界中主要通过啮齿动物和鸟类宿主维持。一个广泛但未经测试的概念假设，即在 菌株中的宿主关联与赋予对补体逃避的功能遗传变异有关，补体是脊椎动物血清中的一种先天防御机制。在这里，我们根据 20 株在啮齿动物和禽类 LD 模型的血清和/或血液以及远端组织中的存活率，将它们分为三组依赖补体的宿主关联表型。对这些菌株的系统发育基因组分析进一步将包括 在内的几个基因家族和位点与宿主特异性的补体逃避表型相关联。这种多方面的研究为进一步确定宿主关联的决定因素铺平了道路，为宿主-病原体相互作用提供了机制上的见解。
