title: Comparative Genomic Analyses of the Moraxella catarrhalis Serosensitive and Seroresistant Lineages Demonstrate Their Independent Evolution.
abstract: The bacterial speciesMoraxella catarrhalishas 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 aresui 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.
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA Center for Genomic Sciences and Center for Advanced Microbial Processing, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA Center for Genomic Sciences, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Earl
authors.affiliation: Present address: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Stefan P W
authors.initials: SP
authors.lastname: de Vries
authors.affiliation: Center for Genomic Sciences, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA.
authors.forename: Azad
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Center for Genomic Sciences, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA.
authors.forename: Evan
authors.initials: E
authors.lastname: Powell
authors.affiliation: Center for Genomic Sciences, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Schultz
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Peter W M
authors.initials: PW
authors.lastname: Hermans
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Hill
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Zhemin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Crystala I
authors.initials: CI
authors.lastname: Constantinidou
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA Center for Genomic Sciences and Center for Advanced Microbial Processing, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA Center for Genomic Sciences, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA Department of Otolaryngology Head and Neck Surgery, Drexel University College of Medicine, Philadelphia, PA.
authors.forename: Fen Z
authors.initials: FZ
authors.lastname: Hu
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands garth.ehrlich@drexelmed.edu hester.bootsma@rivm.nl.
authors.forename: Hester J
authors.initials: HJ
authors.lastname: Bootsma
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA Center for Genomic Sciences and Center for Advanced Microbial Processing, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA Center for Genomic Sciences, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA Department of Otolaryngology Head and Neck Surgery, Drexel University College of Medicine, Philadelphia, PA garth.ehrlich@drexelmed.edu hester.bootsma@rivm.nl.
authors.forename: Garth D
authors.initials: GD
authors.lastname: Ehrlich
mesh_terms: D002460:Cell Line; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D001936:Moraxella catarrhalis / Q000235:genetics* / Q000254:growth & development; D045828:Moraxellaceae Infections / Q000382:microbiology; D005810:Multigene Family; D010802:Phylogeny; D037521:Virulence Factors / Q000235:genetics
chemical_list: D037521:Virulence Factors
keywords: Moraxella catarrhalis; bacteria; comparative genome analysis; distributed genome hypothesis; evolution; pan genome; phylogeny; supragenome