Project description:Asymptomatic colonization of the upper respiratory tract is a common trait of the two exclusive human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis. In vivo models of pathogenic neisserial infections are heterologous systems that permit short-term persistence but do not fully recapitulate infections in humans. Studying Neisseria musculi (Nmus), an oral commensal, in laboratory mice allows investigation of Neisseria-host interactions that avoids host restriction barriers. Nmus produces smooth and rough morphotypes on solid media. We compared the in vitro phenotypes, biofilm transcriptomes, and in vivo colonization patterns and burdens of the Nmus morphotypes. We observed that the two morphotypes differ in biofilm formation, aggregation, pilin production, and transformation frequency in vitro. These phenotypes strongly correlated with differential expression of a set of genes in the Nmus biofilms including those that encoded factors for bacterial attachment. In vivo, the smooth morphotype stably colonized the oral cavities of all inoculated A/J and C57BL/6J mice at higher burdens compared to the rough. Following nasal inoculations, we detected transient Nmus nasal colonization. The smooth morphotype was able to reach higher burdens more quickly in the nasal cavity and on oral swabs following dissemination to the oral cavity. Gut colonization burdens fluctuated over time. Interestingly, both morphotypes colonized the oral cavities of A/Js at higher magnitudes than in C57BL/6Js. Collectively, our results demonstrate that colonization by Nmus can be affected by various factors including Nmus morphotypes, inoculation routes, anatomical niches, and host backgrounds. The Nmus-mouse model can use variable morphotype-host combinations to study the dynamics of neisserial asymptomatic colonization and persistence in multiple extragenital niches.
Project description:Species of the Neisseria genus harbor close relationships with their mamallian hosts, including humans. The outcome of these interactions can result in commensalism, asymptomatic carriage, or acute inflammatory responses. Little is known of the mechanisms Neisseria use to maintain and shape their host niche in the context of asymptomatic infection or long term commensal colonization and persistence. To identify novel host interaction factors contributing to host persistence, a Tn5 transposon library was created in Neisseria musculi, and inoculated into a permissive strain of laboratory mice (CAST/EiJ). At various time points post inoculation, transposon mutants were recovered from fecal and oral samples, and analyzed to identifiy mutants incapable of maintaining a host niche at either site.
Project description:Commensal bacteria are crucial in maintaining host physiological homeostasis, immune system development, and protection against pathogens. Despite their significance, the factors influencing persistent bacterial colonization and their impact on the host still need to be fully understood. Animal models have served as valuable tools to investigate these interactions, but most have limitations. The bacterial genus Neisseria, which includes both commensal and pathogenic species, has been studied from a pathogenicity to humans’ perspective, but lacks models that study immune responses in the context of long-term persistence. Neisseria musculi, a recently described natural commensal of mice, offers a unique opportunity to study long-term host-commensal interactions. In this study, for the first time we have used this model to study the transcriptional, phenotypic, and functional dynamics of immune cell signatures in the mucosal and systemic tissue of mice in response to Neisseria musculi colonization. We found key genes and pathways vital for immune homeostasis in palate tissue, validated by flow cytometry of immune cells from lung, blood and spleen. This study offers a novel avenue for advancing our understanding of host-bacteria dynamics and may provide a platform for developing efficacious interventions against mucosal persistence by pathogenic Neisseria.
Project description:The zur regulon in Neisseria meningitidis was elucidated in the strain MC58 using a zur knockout strain and conditions which activate Zur ( zinc supplementation in the medium)
Project description:Wild type Neisseria gonorrhoea strain FA1090 and N. meningitidis strain MC58 were grown on normal GC plate at either 35 degree celsius (for control samples) or 40 degree celsius (for test samples)
Project description:Neisseria meningitidis is a major cause of bacterial meningitis and septicemia worldwide. Seven new serogroup C meningococci were isolated from two provinces of China in January, 2006. Their PorA VR types were P1.20, 9. Multilocus sequence typing results indicated that they all belonged to ST-7. It is a new serogroup C N. meningitidis sequence type clone identified in China. Here we also present the results of a genomic comparison of these isolates with other 15 N. meningitidis serogroup A and B isolates, which belonged to ST-7, based on comparative genomic hybridization analysis. The data described here would be helpful to monitor the spread of this new serogroup C meningococci sequence type clone in China and worldwide. Keywords: comparative genomic hybridization
Project description:Microarray comparative genome hybridization (mCGH) data was collected from one Neisseria cinerea, two Neisseria lactamica, two Neisseria gonorrhoeae, and 48 Neisseria meningitidis isolates. For N. meningitidis, these isolates are from diverse clonal complexes, invasive and carriage strains, and all major serogroups. The microarray platform represented N. meningitidis strains MC58, Z2491, and FAM18 and N. gonorrhoeae FA1090.