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A Natural Mouse Model for Neisseria Colonization.

ABSTRACT: Commensals are important for the proper functioning of multicellular organisms. How a commensal establishes persistent colonization of its host is little understood. Studies of this aspect of microbe-host interactions are impeded by the absence of an animal model. We have developed a natural small animal model for identifying host and commensal determinants of colonization and of the elusive process of persistence. Our system couples a commensal bacterium of wild mice, Neisseria musculi, with the laboratory mouse. The pairing of a mouse commensal with its natural host circumvents issues of host restriction. Studies are performed in the absence of antibiotics, hormones, invasive procedures, or genetic manipulation of the host. A single dose of N. musculi, administered orally, leads to long-term colonization of the oral cavity and gut. All mice are healthy. Susceptibility to colonization is determined by host genetics and innate immunity. For N. musculi, colonization requires the type IV pilus. Reagents and powerful tools are readily available for manipulating the laboratory mouse, allowing easy dissection of host determinants controlling colonization resistance. N. musculi is genetically related to human-dwelling commensal and pathogenic Neisseria and encodes host interaction factors and vaccine antigens of pathogenic Neisseria Our system provides a natural approach for studying Neisseria-host interactions and is potentially useful for vaccine efficacy studies.

SUBMITTER: Ma M

PROVIDER: S-EPMC5913851 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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A Natural Mouse Model for Neisseria Colonization.

Ma Mancheong M Powell Daniel A DA Weyand Nathan J NJ Rhodes Katherine A KA Rendón María A MA Frelinger Jeffrey A JA So Magdalene M

Infection and immunity 20180423 5

Commensals are important for the proper functioning of multicellular organisms. How a commensal establishes persistent colonization of its host is little understood. Studies of this aspect of microbe-host interactions are impeded by the absence of an animal model. We have developed a natural small animal model for identifying host and commensal determinants of colonization and of the elusive process of persistence. Our system couples a commensal bacterium of wild mice, <i>Neisseria musculi</i>, ...[more]

PMID: 29440372

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Project description:Chronic wound infections are increasingly recognized to be dynamic and polymicrobial in nature, necessitating the development of wound models which reflect the complexities of infection in a non-healing wound. Wound slough isolated from human chronic wounds and transferred to mice was recently shown to create polymicrobial infection in mice, and there is potential this tool may be improved by cryogenic preservation. The purpose of this study was to investigate the application of cryogenic preservation to transferring polymicrobial communities, specifically by quantifying the effects of cryopreservation and wound microbiome transplantation. Slough from an established murine polymicrobial surgical excision model and five patients were subjected to three preservation strategies: refrigeration until infection, freezing in liquid nitrogen, or freezing in liquid nitrogen with glycerol solution prior to infection in individual mice. Four days following inoculation onto mice, wound microbiota were quantified using either culture isolation or by 16s rRNA gene community profiling and quantitative PCR. Cryogenic preservation did not significantly reduce bacterial viability. Reestablished microbial communities were significantly associated with patient of origin as well as host context (i.e., originally preserved from a patient versus mouse infection). Whereas preservation treatment did not significantly shape community composition, the transfers of microbiomes from human to mouse were characterized by reduced diversity and compositional changes. These findings indicated that changes should be expected to occur to community structure after colonization, and that compositional change is likely due to the rapid change in infection context as opposed to preservation strategy. Furthermore, species that were present in higher relative abundance in wound inoculate were more likely to colonize subsequent wounds, and wound inoculate with higher bacterial load established wound communities that were more compositionally similar. Results inform expectations for the complementation of chronic wound in vivo modeling with cryogenic preservation archives.

Project description:UnlabelledCompetitive interactions between Streptococcus pneumoniae strains during host colonization could influence the serotype distribution in nasopharyngeal carriage and pneumococcal disease. We evaluated the competitive fitness of strains of serotypes 6B, 14, 19A, 19F, 23F, and 35B in a mouse model of multiserotype carriage. Isogenic variants were constructed using clinical strains as the capsule gene donors. Animals were intranasally inoculated with a mixture of up to six pneumococcal strains of different serotypes, with separate experiments involving either clinical isolates or isogenic capsule-switch variants of clinical strain TIGR4. Upper-respiratory-tract samples were repeatedly collected from animals in order to monitor changes in the serotype ratios using quantitative PCR. A reproducible hierarchy of capsular types developed in the airways of mice inoculated with multiple strains. Serotype ranks in this hierarchy were similar among pneumococcal strains of different genetic backgrounds in different strains of mice and were not altered when tested under a range of host conditions. This rank correlated with the measure of the metabolic cost of capsule synthesis and in vitro measure of pneumococcal cell surface charge, both parameters considered to be predictors of serotype-specific fitness in carriage. This study demonstrates the presence of a robust competitive hierarchy of pneumococcal serotypes in vivo that is driven mainly, but not exclusively, by the capsule itself.ImportanceStreptococcus pneumoniae (pneumococcus) is the leading cause of death due to respiratory bacterial infections but also a commensal frequently carried in upper airways. Available vaccines induce immune responses against polysaccharides coating pneumococcal cells, but with over 90 different capsular types (serotypes) identified, they can only target strains of the selected few serotypes most prevalent in disease. Vaccines not only protect vaccinated individuals against disease but also protect by reducing carriage of vaccine-targeted strains to induce herd effects across whole populations. Unfortunately, reduction in the circulation of vaccine-type strains is offset by increase in carriage and disease from nonvaccine strains, indicating the importance of competitive interactions between pneumococci in shaping the population structure of this pathogen. Here, we showed that the competitive ability of pneumococcal strains to colonize the host strongly depends on the type of capsular polysaccharide expressed by pneumococci and only to a lesser degree on strain or host genetic backgrounds or on variation in host immune responses.

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A Natural Mouse Model for Neisseria Colonization.

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A Natural Mouse Model for Neisseria Colonization.

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