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Neisseria lactamica  is a harmless coloniser of the infant respiratory tract, and has a mutually-excluding relationship with the pathogen  Neisseria meningitidis . Here we report controlled human infection with genomically-defined  N. lactamica  and subsequent bacterial microevolution during 26 weeks of colonisation. We find that most mutations that occur during nasopharyngeal carriage are transient indels within repetitive tracts of putative phase-variable loci associated with host-microbe interactions ( pgl  and  lgt ) and iron acquisition ( fetA  promotor and  hpuA ). Recurrent polymorphisms occurred in genes associated with energy metabolism ( nuoN ,  rssA ) and the CRISPR-associated  cas1 . A gene encoding a large hypothetical protein was often mutated in 27% of the subjects. In volunteers who were naturally co-colonised with meningococci, recombination altered allelic identity in  N. lactamica  to resemble meningococcal alleles, including loci associated with metabolism, outer membrane proteins and immune response activators. Our results suggest that phase variable genes are often mutated during carriage-associated microevolution.

Microevolution of Neisseria lactamica during nasopharyngeal colonisation induced by controlled human infection