Comparative Genomic Analyses of theMoraxella catarrhalisSerosensitive 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] and serosensitive [SS]) with separate evolutionary histories based on several molecular typing methods, whereas 16S ribotyping has suggested an additional split within the SS lineage. Previously, we characterized whole-genome sequences of 12 SR-lineage isolates, which revealed a relatively small supragenome when compared with other opportunistic nasopharyngeal pathogens, suggestive of a relatively short evolutionary history. Here, we performed whole-genome sequencing on 18 strains from both ribotypes 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 distributed genes; and by an alignment of concatenated core sequences irrespective of gene annotation. All these methods show that the SS lineage has much longer interstrain branches than the SR lineage indicating that this lineage has likely been evolving either longer or faster than the SR lineage. There is evidence of extensive horizontal gene transfer (HGT) within both of these lineages, and to a lesser degree between them. In particular, we identified very high rates of HGT between these two lineages for ß-lactamase genes. The four divergent strains are sui generis, being much more distantly related to both the SR and SS groups than these other two groups are to each other. Based on average nucleotide identities, gene content, GC content, and genome size, this group could be 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 common core genome, average nucleotide identity values, GC content, and genome size. 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.

Virulence factors of Moraxella catarrhalis outer membrane vesicles are major targets for cross-reactive antibodies and have adapted during evolution

“…This species is thought to be composed of two distinct lineages, namely the more pathogenic sero-resistant (SR) strains and the less pathogenic sero-sensitive (SS) ones 7 , 8 . These two groups of strains show separate evolutionary histories and contain a distinct subset of lineage-specific genes, 33 and 49, respectively 9 . Some of the genes unique to the SR lineage are involved in phosphate metabolism but others do not have assigned functions.…”

Moraxella catarrhalis Restriction-Modification Systems are Associated with Phylogenetic Lineage and Disease

“…1 ), and although currently classified as M. catarrhalis , are predicted to represent a different species or subspecies ( Wirth et al. 2007 ; Earl et al. 2016 ).…”

“…2017 ). Comparative supragenome analysis of thirteen RB1 and eighteen RB2/3 genomes demonstrated that virulence factors responsible for adherence and serum resistance are found in the core M. catarrhalis genome, with no virulence factors found solely in either lineage ( Earl et al. 2016 ).…”

A Cation-Binding Surface Protein as a Vaccine Antigen To Prevent Moraxella catarrhalis Otitis Media and Infections in Chronic Obstructive Pulmonary Disease

“…The 3 remaining strains identified as M. catarrhalis showed lower homologies. These strains are variant strains and, based on genome sequences, will soon be reclassified as a different species (44).…”