A filamentous bacteriophage termed the Meningococcal Disease Associated (MDA) phage is associated with Neisseria meningitidis clades which cause invasive meningococcal disease. MDA phage improves mucosal colonization of the nasopharynx by meningococci and thus increasing the incidence of bloodstream invasion associated with meningococcal carriage. We recently recovered a gonococcal isolate (ExNg63) from a rare case of gonococcal meningitis and whole genome sequencing revealed that this isolate possessed a region with 90% similarity to the MDA phage found in N. meningitidis. Sanger sequencing confirmed that the entire MDA-like phage was intact in the genome of ExNg63. This is the first indication that MDA-like phages may not be restricted to N. meningitidis. Therefore, to understand the genetic diversity and distribution of MDA-like phages, we examined the distribution, prevalence and genetic diversity of MDA-like phages in Neisseriaceae.
Closed genomes of 44 N. meningitidis, 28 N. gonorrhoeae, 2 N. lactamica and 17 commensal Neisseria species were collected from the NCBI database and BIGSdb. Filamentous prophages were defined as a set of genes that have the size and genetic organization similar to the MDA phage in Neisseria meningitidis Z2491 or Ngo6-8 in Neisseria gonorrhoeae FA1090. A maximum likelihood phylogenetic tree was constructed using MEGA7 with 500 bootstrap replicates while heirBAPS was used to define genetic population groups of prophages using MAFFT aligned prophage sequences.
One hundred and sixty filamentous prophages were detected in the dataset and population structure analysis using heirBAPS revealed that the putative gonococcal MDA-like phages and a putative MDA-like phage in N. lactamica formed a structure group with meningococcal MDA-phage. However, only 292 of 3800 gonococcal isolates available at BIGSdb possessed a complete or partial MDA-like sequence suggesting that acquisition of MDA-like phages is rare in this species. These data suggest that prophages similar to the meningococcal MDA phage are present in N. gonorrhoeae and N. lactamica and more work is required to determine whether MDA-like phages act as accessory colonization factors in these species.