Comparative genomic analyses of the moraxella catarrhalis serosensitive and seroresistant lineages demonstrate their independent evolution

Abstract

The bacterial species Moraxella catarrhalis has been hypothesized as being composed of two distinct lineages (referred to as the seroresistant [SR] andserosensitive [SS]) with separate evolutionary historiesbasedonseveralmolecular typing methods, whereas16S ribotyping has suggested an additional split within the SS lineage. Previously, we characterized whole-genome sequences of 12 SRlineage isolates,which revealed a relatively small supragenomewhencomparedwithotheropportunisticnasopharyngeal pathogens, suggestiveof a relatively short evolutionary history. Here,weperformedwhole-genomesequencingon18strains frombothribotypes of the SS lineage, an additional SR strain, as well as four previously identified highly divergent strains based on multilocus sequence typing analyses. All 35 strains were subjected to a battery of comparative genomic analyses which clearly show that there are three lineages-the SR, SS, and the divergent. The SR and SS lineages are closely related, but distinct from each other based on three different methods of comparison: Allelic differences observed among core genes; possession of lineage-specific sets of core and distributedgenes; andby analignmentof concatenated core sequences irrespective of gene annotation.All thesemethods showthat the SS lineage has much longer interstrain branches than the SR lineage indicating that this lineage has likely been evolving either longeror faster than the SR lineage. There is evidenceof extensivehorizontal gene transfer (HGT) within bothof these lineages, and to a lesser degree between them. In particular, we identified very high rates of HGT between these twolineages for ß-lactamase genes. The fourdivergent strains are suigeneris,beingmuchmore distantly related toboth the SRandSS groups thanthese other twogroups are toeachother.Basedonaveragenucleotide identities,genecontent,GCcontent,andgenomesize, this groupcouldbe considered as a separate taxonomic group. The SR and SS lineages, although distinct, clearly form a single species based on multiple criteria including a large commoncore genome, average nucleotide identity values,GCcontent, and genomesize. Although neither of these lineages arose from within the other based on phylogenetic analyses, the question of how and when these lineages split and then subsequently reunited in the human nasopharynx is explored.