In vitro and transcriptomic variation in Neisseria musculi morphotypes correlate with colonization variability and persistence in vivo

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. Overall design: Six data sets in total. Three replicates of biofilms formed by the two N. musculi morphotypes. Two separate analyses were performed. One analysis was done using two replicates for each condition (GSM5582130 and GSM5582131 [smooth] and GSM5582134 and GSM5582135 [rough]) and one analysis was done using all three replicates per condition. Samples include the normalized data for the two replicate analysis and the three replicate analysis. The DESeq output files for each analysis are available on foot of this record.