title: Comparative Genomics Reveal That Host-Innate Immune Responses Influence the Clinical Prevalence of Legionella pneumophila Serogroups.
abstract: Legionella pneumophila is the primary etiologic agent of legionellosis, a potentially fatal respiratory illness. Amongst the sixteen described L. pneumophila serogroups, a majority of the clinical infections diagnosed using standard methods are serogroup 1 (Sg1). This high clinical prevalence of Sg1 is hypothesized to be linked to environmental specific advantages and/or to increased virulence of strains belonging to Sg1. The genetic determinants for this prevalence remain unknown primarily due to the limited genomic information available for non-Sg1 clinical strains. Through a systematic attempt to culture Legionella from patient respiratory samples, we have previously reported that 34% of all culture confirmed legionellosis cases in Ontario (n = 351) are caused by non-Sg1 Legionella. Phylogenetic analysis combining multiple-locus variable number tandem repeat analysis and sequence based typing profiles of all non-Sg1 identified that L. pneumophila clinical strains (n = 73) belonging to the two most prevalent molecular types were Sg6. We conducted whole genome sequencing of two strains representative of these sequence types and one distant neighbour. Comparative genomics of the three L. pneumophila Sg6 genomes reported here with published L. pneumophila serogroup 1 genomes identified genetic differences in the O-antigen biosynthetic cluster. Comparative optical mapping analysis between Sg6 and Sg1 further corroborated this finding. We confirmed an altered O-antigen profile of Sg6, and tested its possible effects on growth and replication in in vitro biological models and experimental murine infections. Our data indicates that while clinical Sg1 might not be better suited than Sg6 in colonizing environmental niches, increased bloodstream dissemination through resistance to the alternative pathway of complement mediated killing in the human host may explain its higher prevalence.
authors.affiliation: Public Health Ontario, Toronto, Ontario, Canada ; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mohammad Adil
authors.initials: MA
authors.lastname: Khan
authors.forename: Natalie
authors.initials: N
authors.lastname: Knox
authors.forename: Akriti
authors.initials: A
authors.lastname: Prashar
authors.forename: David
authors.initials: D
authors.lastname: Alexander
authors.forename: Mena
authors.initials: M
authors.lastname: Abdel-Nour
authors.forename: Carla
authors.initials: C
authors.lastname: Duncan
authors.forename: Patrick
authors.initials: P
authors.lastname: Tang
authors.forename: Hajera
authors.initials: H
authors.lastname: Amatullah
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Dos Santos
authors.forename: Nathalie
authors.initials: N
authors.lastname: Tijet
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
authors.forename: Christine
authors.initials: C
authors.lastname: Pourcel
authors.forename: Gary
authors.initials: G
authors.lastname: Van Domselaar
authors.forename: Mauricio
authors.initials: M
authors.lastname: Terebiznik
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Ensminger
authors.forename: Cyril
authors.initials: C
authors.lastname: Guyard
mesh_terms: D048248:Acanthamoeba castellanii / Q000382:microbiology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms; D004195:Disease Models, Animal; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D016952:Legionella pneumophila / Q000145:classification / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D007877:Legionnaires' Disease / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D019081:O Antigens / Q000096:biosynthesis / Q000235:genetics; D009864:Ontario; D010802:Phylogeny; D015995:Prevalence; D011487:Protein Conformation; D020543:Proteome; D065288:Serogroup; D020298:U937 Cells
chemical_list: D001426:Bacterial Proteins; D019081:O Antigens; D020543:Proteome