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.

The Commensal Neisseria musculi Modulates Host Innate Immunity To Promote Oral Colonization

“…Indeed, much of the work of the commensal segmented filamentous bacteria relies only on colonization following antibiotic pretreatment (11). Recent work in our laboratory has established a new mouse model for colonization using the recently described mouse commensal Neisseria musculi (12, 13). N. musculi was isolated from the oral cavity of healthy wild-caught mice.…”

UKMenCar4: A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence

“…Humans are the sole known reservoir for the meningococcus and, as such, carriage surveys can provide information about the human reservoir and transmission dynamics that have implications for disease epidemiology. Studying the physiological circumstances that promote bacterial invasion rather than colonization is difficult as human challenge models are not appropriate, but both laboratory 36 and mouse 37, 38 models have been developed to address these research questions in vitro . Despite this, real life population dynamics are relatively easy to measure and monitor through large carriage surveys, though to obtain a sample representative of the whole population, studies need to be of sufficient magnitude and well-resourced.…”

Pathogenic Interplay Between Chlamydia trachomatis and Neisseria gonorrhoeae that Influences Management and Control Efforts—More Questions than Answers?

“…Uruburuella suis, a novel species in the family Neisseriaceae, was isolated from pigs with pneumonia and pericarditis in 2005 [89••, 98]. A new commensal Neisseria species (N. musculi) has also been recently identified in the wild house mouse [99,100]. N. musculi can be cultured and transformed to produce knockout and gene-complemented strains and colonizes the gut and oral mucosa of C57/B6 mice without producing overt disease.…”

“…N. musculi colonization in mice requires neither estradiol or antibiotic treatment nor expression of human-specific receptors. The N. musculi genome also contains predicted homologs for several NG and N. meningitidis virulence factor-encoding genes [100]. Because CM establishes gastrointestinal infection in mice via the oral route [101,102], co-infecting mice orally with CM and N. musculi should be relatively straightforward.…”