模式动物在共生微生物研究中的作用

共生微生物是一类定殖于宿主体表或体内, 可执行宿主本身无法完成的功能, 并依赖于宿主所提供的生长环境的微生物。众多研究表明, 人体肠道共生微生物与免疫、营养、代谢, 甚至精神健康等生理功能密切相关, 是重要的“微生物器官”。在早期的肠道微生物研究中, 模式动物就已经作为研究工具被使用。随着肠道微生物研究的不断深入, 模式动物作为不可替代的研究对象发挥了越来越重要的作用。本综述主要对几种重要的模式动物如斑马鱼(Danio rerio)、小鼠(Mus musculus)、猪(Sus scrofa domesticus)和猕猴(Macaca mulatta)在肠道微生物研究中的应用进行了总结, 介绍了各种模式动物的发展过程及特点, 各自在应用于研究时的优缺点, 以及利用这些动物模型在共生微生物领域所取得的一些标志性的科研成果。同时, 也就近年来在共生微生物领域新兴的一些模式生物如蜜蜂(Apis)、果蝇(Drosophila)、秀丽隐杆线虫(Caenorhabditis elegans)等进行了一些探讨。旨在让该领域的研究者们了解模式动物与人体在共生微生物方面的异同, 为更好地利用这一研究工具提供参考。     

Bioprospecting for Microbial Endophytes and Their Natural Products

Endophytic microorganisms are to be found in virtually every plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to slightly pathogenic. Because of what appears to be their contribution to the host plant, the endophytes may produce a plethora of substances of potential use to modern medicine, agriculture, and industry. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation, culture, purification, and characterization of some choice endophytes in the recent past. The potential prospects of finding new drugs that may be effective candidates for treating newly developing diseases in humans, plants, and animals are great.     

Bioprospecting for microbial endophytes and their natural products.

Endophytic microorganisms are to be found in virtually every plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to slightly pathogenic. Because of what appears to be their contribution to the host plant, the endophytes may produce a plethora of substances of potential use to modern medicine, agriculture, and industry. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation, culture, purification, and characterization of some choice endophytes in the recent past. The potential prospects of finding new drugs that may be effective candidates for treating newly developing diseases in humans, plants, and animals are great.     

Plant-Associated Symbiotic Burkholderia Species Lack Hallmark Strategies Required in Mammalian Pathogenesis

Burkholderia is a diverse and dynamic genus, containing pathogenic species as well as species that form complex interactions with plants. Pathogenic strains, such as B. pseudomallei and B. mallei, can cause serious disease in mammals, while other Burkholderia strains are opportunistic pathogens, infecting humans or animals with a compromised immune system. Although some of the opportunistic Burkholderia pathogens are known to promote plant growth and even fix nitrogen, the risk of infection to infants, the elderly, and people who are immunocompromised has not only resulted in a restriction on their use, but has also limited the application of non-pathogenic, symbiotic species, several of which nodulate legume roots or have positive effects on plant growth. However, recent phylogenetic analyses have demonstrated that Burkholderia species separate into distinct lineages, suggesting the possibility for safe use of certain symbiotic species in agricultural contexts. A number of environmental strains that promote plant growth or degrade xenobiotics are also included in the symbiotic lineage. Many of these species have the potential to enhance agriculture in areas where fertilizers are not readily available and may serve in the future as inocula for crops growing in soils impacted by climate change. Here we address the pathogenic potential of several of the symbiotic Burkholderia strains using bioinformatics and functional tests. A series of infection experiments using Caenorhabditis elegans and HeLa cells, as well as genomic characterization of pathogenic loci, show that the risk of opportunistic infection by symbiotic strains such as B. tuberum is extremely low.     

The challenges of modeling mammalian biocomplexity

Understanding the relationships between human genetic factors, the risks of developing major diseases and the molecular basis of drug efficacy and toxicity is a fundamental problem in modern biology. Predicting biological outcomes on the basis of genomic data is a major challenge because of the interactions of specific genetic profiles with numerous environmental factors that may conditionally influence disease risks in a nonlinear fashion. 'Global' systems biology attempts to integrate multivariate biological information to better understand the interaction of genes with the environment. The measurement and modeling of such diverse information sets is difficult at the analytical and bioinformatic modeling levels. Highly complex animals such as humans can be considered 'superorganisms' with an internal ecosystem of diverse symbiotic microbiota and parasites that have interactive metabolic processes. We now need novel approaches to measure and model metabolic compartments in interacting cell types and genomes that are connected by cometabolic processes in symbiotic mammalian systems.     

The Entomopathogenic Nematode-Bacterium Complex: Biology, Life Cycle and Vertebrate Safety

This paper reports on several aspects of the taxonomy and biology of the symbiotic bacteria, Xenorhabdus spp. and Photorhabdus spp., associated with entomopathogenic nematodes (EPNs), which may be used to define the boundaries with pathogenic bacteria of medical, veterinary or agronomic importance. All the result of tests undertaken to assess the effects of these bacteria on warm-blooded vertebrates were negative, indicating that the bacteri would pose no hazard to vertebrates in practice. Non-symbiotic microorganisms are also associated occasionally with EPNs, and some of them, e.g Providencia rettgeri, belong to taxa which include opportunistic pathogens of man. This review emphasizes that the relationship between these non-symbiotic bacteria and nematodes cannot be considered to be a risk for humans because they do not support the growth of nematodes during long-term mass rearing or they do not persist during storage of nematodes, so their purposeful use is necessarily excluded for industrial production. Good practice by biotechnology laboratories can avoid such contaminants. However, commercial producers should be aware of the possible occurrence of human opportunistic pathogens and prevent such contaminations by establishing monoxenic symbiotic cultures. The pathogenic properties of both partners of the normal bacterium-EPN complex are examined with respect to the risks they pose to human and vertebrate health and to the environment. It is concluded that no risk to warm-blooded animals or plants is related to the use of EPNs in biological control.     

Microeukaryotes in animal and plant microbiomes: Ecologies of disease?

Studies of animal and plant microbiomes are burgeoning, but the majority of these focus on bacteria and rarely include microeukaryotes other than fungi. However, there is growing evidence that microeukaryotes living on and in larger organisms (e.g. plants, animals, macroalgae) are diverse and in many cases abundant. We present here a new combination of ‘anti-metazoan’ primers: 574*f–UNonMet_DB that amplify a wide diversity of microeukaryotes including some groups that are difficult to amplify using other primer combinations. While many groups of microeukaryotic parasites are recognised, myriad other microeukaryotes are associated with hosts as previously unknown parasites (often genetically divergent so difficult to amplify using standard PCR primers), opportunistic parasites, commensals, and other ecto- and endo-symbionts, across the ‘symbiotic continuum'. These fulfil a wide range of roles from pathogenesis to mutually beneficial symbioses, but mostly their roles are unknown and likely fall somewhere along this spectrum, with the potential to switch the nature of their interactions with the host under different conditions. The composition and dynamics of host-associated microbial communities are also increasingly recognised as important moderators of host health. This ‘pathobiome’ approach to understanding disease is beginning to supercede a one-pathogen-one-disease paradigm, which cannot sufficiently explain many disease scenarios.     

Symbiovars in rhizobia reflect bacterial adaptation to legumes

Legume specificity is encoded in rhizobial genetic elements that may be transferred among species and genera. Dissemination (by lateral transfer) of gene assemblies dictating host range accounts for the existence of the same biological variant (biovar) in distinct microbiological species. Different alternative biovars may exist in a single species expanding their adaptation to different niches (legume nodules). A review of all reported biovars is presented. Instead of the term biovar, symbiotic variant (symbiovar) is proposed as a parallel term to pathovar in pathogenic bacteria. Symbiovars should be determined based on the symbiotic capabilities in plant hosts, distinguished by the differences in host range and supported by symbiotic gene sequence information.     

Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution

We present here the hologenome theory of evolution, which considers the holobiont (the animal or plant with all of its associated microorganisms) as a unit of selection in evolution. The hologenome is defined as the sum of the genetic information of the host and its microbiota. The theory is based on four generalizations: (1) All animals and plants establish symbiotic relationships with microorganisms. (2) Symbiotic microorganisms are transmitted between generations. (3) The association between host and symbionts affects the fitness of the holobiont within its environment. (4) Variation in the hologenome can be brought about by changes in either the host or the microbiota genomes; under environmental stress, the symbiotic microbial community can change rapidly. These points taken together suggest that the genetic wealth of diverse microbial symbionts can play an important role both in adaptation and in evolution of higher organisms. During periods of rapid changes in the environment, the diverse microbial symbiont community can aid the holobiont in surviving, multiplying and buying the time necessary for the host genome to evolve. The distinguishing feature of the hologenome theory is that it considers all of the diverse microbiota associated with the animal or the plant as part of the evolving holobiont. Thus, the hologenome theory fits within the framework of the 'superorganism' proposed by Wilson and Sober.     

无菌动物及其在微生物与宿主互作机制研究中的应用

无菌动物是指通过现代技术手段在其体内外的任何部位均检测不出细菌、真菌、放线菌、支原体、衣原体、螺旋体、立克次氏体、病毒、原生动物和寄生虫的动物。无菌动物因其不携带任何微生物,可转化为携带特定微生物的动物,同时因其免疫系统处于休眠状态,对微生物感染异常敏感,可建立多种悉生动物模型,用于特定微生物感染实验和致病机制研究。此外,无菌动物作为关键工具,是研究菌群与疾病关系的核心,在微生物与宿主健康、疾病和感染机制研究过程中,起着不可替代的作用。本文将对无菌动物及其在微生物与宿主互作机制研究中的应用进行简要综述。     

Peptidoglycan recognition proteins: modulators of the microbiome and inflammation

All animals, including humans, live in symbiotic association with microorganisms. The immune system accommodates host colonization by the microbiota, maintains microbiota-host homeostasis and defends against pathogens. This Review analyses how one family of antibacterial pattern recognition molecules - the peptidoglycan recognition proteins - has evolved a fascinating variety of mechanisms to control host interactions with mutualistic, commensal and parasitic microorganisms to benefit both invertebrate and vertebrate hosts.     

Molecular evolution of the fungi: human pathogens.

The morphological, ecological, and clinical diversity among ascomycete fungi that are pathogenic to humans suggest that the potential for pathogenicity may have arisen multiple times within these higher fungi. We have obtained 18S ribosomal DNA sequences from a diverse group of human pathogenic fungi in order to determine their evolutionary origins. The fungi studied include a skin pathogen that is confined to humans (Trichophyton rubrum) and three systemic, facultative parasites that cause histoplasmosis (Histoplasma capsulatum), blastomycosis (Blastomyces dermatitidis) and coccidioidomycosis (Coccidioides immitis) in humans and other higher animals. Also included in our analysis are representatives of non-pathogenic fungi, as well as two opportunistic pathogens, Pneumocystis carinii and Candida albicans, that cause severe disease in immunocompromised individuals, especially those with AIDS. Two of the fungi we sequenced, T. rubrum and C. immitis, are limited to asexual modes of reproduction and therefore lack the sexual structures that are most useful for evolutionary comparison as well as being essential for classification among the higher fungi. Coccidioides immitis is particularly problematic owing to its contradictory and confusing asexual morphologies, which have caused it to be placed in three fungal classes and the protista. Our analysis shows that the specialized, superficial parasite and the systemic, facultative parasites, including C. immitis, are closely related ascomycetes, which clearly demonstrates the power of molecular characters to compensate for missing or confusing reproductive morphology. Analysis also shows that the opportunistic pathogens are more distantly related, with the likely explanation that pathogenicity has arisen more than once within the Ascomycetes.     

Insect endosymbionts: manipulators of insect herbivore trophic interactions?

Throughout their evolutionary history, insects have formed multiple relationships with bacteria. Although many of these bacteria are pathogenic, with deleterious effects on the fitness of infected insects, there are also numerous examples of symbiotic bacteria that are harmless or even beneficial to their insect host. Symbiotic bacteria that form obligate or facultative associations with insects and that are located intracellularly in the host insect are known as endosymbionts. Endosymbiosis can be a strong driving force for evolution when the acquisition and maintenance of a microorganism by the insect host results in the formation of novel structures or changes in physiology and metabolism. The complex evolutionary dynamics of vertically transmitted symbiotic bacteria have led to distinctive symbiont genome characteristics that have profound effects on the phenotype of the host insect. Symbiotic bacteria are key players in insect–plant interactions influencing many aspects of insect ecology and playing a key role in shaping the diversification of many insect groups. In this review, we discuss the role of endosymbionts in manipulating insect herbivore trophic interactions focussing on their impact on plant utilisation patterns and parasitoid biology.     

Helicobacter equorum: prevalence and significance for horses and humans

Helicobacter equorum colonizes the caecum, colon and rectum of horses. The agent is highly prevalent in <6-month-old foals. In adult horses, the prevalence of H. equorum seems to be rather low, but these animals may harbour low, subdetectable numbers of this microorganism in their intestines. So far, no association could be made between the presence of H. equorum and clinical disease or intestinal lesions in adult horses. Further research is necessary to elucidate the pathogenic potential of this bacterial species towards young foals. Helicobacter equorum DNA was not detected in human faeces, indicating that this microorganism does not commonly spread from horses towards humans.     

Brucella adaptation and survival at the crossroad of metabolism and virulence

"In vivo" bacterial nutrition, i.e. the nature of the metabolic network and substrate(s) used by bacteria within their host, is a fundamental aspect of pathogenic or symbiotic lifestyles. A typical example are the Brucella spp., facultative intracellular pathogens responsible for chronic infections of animals and humans. Their virulence relies on their ability to modulate immune response and the physiology of host cells, but the fine-tuning of their metabolism in the host during infection appears increasingly crucial. Here we review new insights on the links between Brucella virulence and metabolism, pointing out the need to investigate both aspects to decipher Brucella infectious strategies.     

环境胁迫下内生菌与宿主代谢相互作用研究进展

植物体内成分是实时反映其生理状态的最直接指标,是其遭受生物或非生物胁迫应激状态的体现,微生物与植物的共生抗逆亦由代谢的重置与调控得以实现。内生菌可以自身细胞功能或代谢产物调控宿主代谢,其自身可产生独特的、显著区别于宿主的代谢成分参与抗逆;而宿主内环境的长期“驯化”亦可改变内生菌的表型和代谢。较全面地分析了植物与微生物共生抗逆在代谢层面的相互作用,旨为同一领域工作者提供有价值的参考。     

The symbiotic microflora associated with the tegument of proteocephalidean cestodes and the intestines of their fish hosts

The indigenous symbiotic microflora associated with the tegument of proteocephalidean cestodes and the intestines of their fish hosts has been investigated in morphological and ecological aspects. The indigenous microflora associated with the cestode tegument consists of the nannobacteria population, which was present obligatorily on the surface of tegument, and the "deep microflora". The deep microflora associates with some few species of parasites only. Each individual host-parasite micro-biocenosis includes specific indigenous symbiotic microorganisms, with the differing microfloras of host intestine and parasite. Physiology, biochemistry and/or diet of hosts apparently influence on the symbiotic microflora's structure of parasites. The least bacteria abundance and diversity of their morphotypes were observed in the parasites from baby fishes. The diversity and abundance of bacteria were increased with the fish host ageing and the formation of the definitive structure of its intestine. It is an evidence of the gradual invading of the intestinal parasites (cestodes) tegument by bacterial cells. The invading is realized on the base of the microflora that was present in the food of fish host. The symbiotic microflora has specific morphological features, can regulate the homeostasis of the cestodes and fish hosts and also can maintain equilibrium of alimentary and immune interrelations in the host-parasite system.     

宏基因组学在人和动物胃肠道微生物研究中的应用进展

人和动物胃肠道存在大量微生物群落,这些微生物是与宿主长期共同进化的结果,并且同宿主的健康和疾病密切相关,因此胃肠道微生物研究已成为当今的热点研究领域。宏基因组学技术在这一领域的应用,使我们不仅能够对胃肠道微生物群落结构及多样性进行分析,还能进一步深入了解其代谢功能,开发和利用潜在的微生物及其基因资源。文中结合我们的研究工作,综述了宏基因组学在人和动物胃肠道微生物研究中的应用,同时着重介绍宏基因组研究的生物信息学技术。     

Genomic and evolutionary comparisons of diazotrophic and pathogenic bacteria of the order Rhizobiales

Background

Species belonging to the Rhizobiales are intriguing and extensively researched for including both bacteria with the ability to fix nitrogen when in symbiosis with leguminous plants and pathogenic bacteria to animals and plants. Similarities between the strategies adopted by pathogenic and symbiotic Rhizobiales have been described, as well as high variability related to events of horizontal gene transfer. Although it is well known that chromosomal rearrangements, mutations and horizontal gene transfer influence the dynamics of bacterial genomes, in Rhizobiales, the scenario that determine pathogenic or symbiotic lifestyle are not clear and there are very few studies of comparative genomic between these classes of prokaryotic microorganisms trying to delineate the evolutionary characterization of symbiosis and pathogenesis.

Results

Non-symbiotic nitrogen-fixing bacteria and bacteria involved in bioremediation closer to symbionts and pathogens in study may assist in the origin and ancestry genes and the gene flow occurring in Rhizobiales. The genomic comparisons of 19 species of Rhizobiales, including nitrogen-fixing, bioremediators and pathogens resulted in 33 common clusters to biological nitrogen fixation and pathogenesis, 15 clusters exclusive to all nitrogen-fixing bacteria and bacteria involved in bioremediation, 13 clusters found in only some nitrogen-fixing and bioremediation bacteria, 01 cluster exclusive to some symbionts, and 01 cluster found only in some pathogens analyzed. In BBH performed to all strains studied, 77 common genes were obtained, 17 of which were related to biological nitrogen fixation and pathogenesis. Phylogenetic reconstructions for Fix, Nif, Nod, Vir, and Trb showed possible horizontal gene transfer events, grouping species of different phenotypes.

Conclusions

The presence of symbiotic and virulence genes in both pathogens and symbionts does not seem to be the only determinant factor for lifestyle evolution in these microorganisms, although they may act in common stages of host infection. The phylogenetic analysis for many distinct operons involved in these processes emphasizes the relevance of horizontal gene transfer events in the symbiotic and pathogenic similarity.     

Review: Microbial endocrinology: intersection of microbiology and neurobiology matters to swine health from infection to behavior

From birth to slaughter, pigs are in constant interaction with microorganisms. Exposure of the skin, gastrointestinal and respiratory tracts, and other systems allows microorganisms to affect the developmental trajectory and function of porcine physiology as well as impact behavior. These routes of communication are bi-directional, allowing the swine host to likewise influence microbial survival, function and community composition. Microbial endocrinology is the study of the bi-directional dialogue between host and microbe. Indeed, the landmark discovery of host neuroendocrine systems as hubs of host–microbe communication revealed neurochemicals act as an inter-kingdom evolutionary-based language between microorganism and host. Several such neurochemicals are stress catecholamines, which have been shown to drastically increase host susceptibility to infection and augment virulence of important swine pathogens, including Clostridium perfringens. Catecholamines, the production of which increase in response to stress, reach the epithelium of multiple tissues, including the gastrointestinal tract and lung, where they initiate diverse responses by members of the microbiome as well as transient microorganisms, including pathogens and opportunistic pathogens. Multiple laboratories have confirmed the evolutionary role of microbial endocrinology in infectious disease pathogenesis extending from animals to even plants. More recent investigations have now shown that microbial endocrinology also plays a role in animal behavior through the microbiota–gut–brain axis. As stress and disease are ever-present, intersecting concerns during each stage of swine production, novel strategies utilizing a microbial endocrinology-based approach will likely prove invaluable to the swine industry.