Colistin Sensitivity and Factor H-Binding Protein Expression among Commensal Neisseria Species

Many bacterial carriage studies utilize colistin-containing media to select for Neisseria meningitidis among the diverse human pharyngeal milieu. These studies commonly report the isolation of Neisseria commensal species, with carriage rates of around 1% or less typically observed. Here, we describe the isolation of N. cinerea and N. polysaccharea from pharyngeal swabs using nonselective agar and confirm they are unable to grow on colistin-containing media. We also demonstrated colistin sensitivity among archived Neisseria commensal strains, including N. cinerea, N. polysaccharea, N. mucosa, and N. subflava. The distribution of lptA among these strains indicated that, while the phosphoethanolamine (PEA) transferase encoded by this gene confers colistin resistance, other mechanisms may lead to reduced susceptibility in some lptA-deficient strains. The majority of the N. cinerea and N. polysaccharea isolates expressed medium to very high levels of factor H-binding protein (fHbp), an important meningococcal vaccine antigen. Sequence analysis showed that the commensal fHbp peptide variants were similar in sequence to fHbp variants typically observed among invasive meningococci. Altogether, these results not only suggest that Neisseria commensal strains could be carried at much higher rates than previously reported but also raise questions about the impact of protein-based meningococcal vaccines on these unencapsulated commensals. IMPORTANCE This study highlights the need for further work to accurately determine the pharyngeal carriage prevalence of Neisseria commensal bacteria (e.g., N. cinerea and N. polysaccharea) among the general population. Previous studies have clearly demonstrated the suppressive effect these commensal species can have on meningococcal colonization, and so the carriage prevalence of these species could be an important factor in the spread of meningococci through the population. Furthermore, the surface expression of the meningococcal vaccine antigen factor H-binding protein by many of these commensal strains could have important implications for the use of fHbp-containing vaccines. Carriage of these commensal species may influence the immune response to these vaccines, or conversely, the immune response elicited by vaccination may induce clearance of these potentially important members of the pharyngeal niche.

Automated summary

This study emphasizes the importance of accurately determining the prevalence of Neisseria commensal bacteria, such as N. cinerea and N. polysaccharea, in the general population. Previous research has shown the suppressive effect of these commensal species on meningococcal colonization, highlighting the potential impact of their carriage prevalence on the spread of meningococci. Additionally, the surface expression of the meningococcal vaccine antigen factor H-binding protein by many of these commensal strains may have implications for the use of fHbp-containing vaccines. Carriage of these commensal species could influence the immune response to vaccines or the immune response elicited by vaccination may affect the clearance of these important pharyngeal niche members.