Comparative Genomics Reveal That Host-Innate Immune Responses Influence the Clinical Prevalence of Legionella pneumophila Serogroups

Autor: Claudia C. dos Santos, Christine Pourcel, Carla Duncan, Natalie C. Knox, David C. Alexander, Hajera Amatullah, Donald E. Low, Gary Van Domselaar, Nathalie Tijet, Mohammad Adil Khan, Mauricio Terebiznik, Akriti Prashar, Mena Abdel-Nour, Alexander W. Ensminger, Patrick Tang, Cyril Guyard
Rok vydání: 2013
Předmět:
Bacterial Diseases
Mouse
Proteome
Protein Conformation
Applied Microbiology
Pathogenesis
Legionella pneumophila
Genome
Mice
Prevalence
Gram Negative
Genome Sequencing
Phylogeny
Ontario
Genetics
Acanthamoeba castellanii
0303 health sciences
Multidisciplinary
biology
O Antigens
Genomics
Animal Models
U937 Cells
Innate Immunity
Bacterial Pathogens
3. Good health
Host-Pathogen Interaction
Variable number tandem repeat
Infectious Diseases
Medical Microbiology
Medicine
Female
Legionnaires' Disease
Research Article
Legionella
Science
Virulence
Serogroup
Microbiology
03 medical and health sciences
Model Organisms
Bacterial Proteins
Phylogenetics
Animals
Humans
Biology
Microbial Pathogens
030304 developmental biology
Whole genome sequencing
Comparative genomics
Evolutionary Biology
Legionellosis
030306 microbiology
Immunity
Computational Biology
Immune Defense
Comparative Genomics
biology.organism_classification
Disease Models
Animal
Emerging Infectious Diseases
Biofilms
Genome
Bacterial
Zdroj: PLoS ONE, Vol 8, Iss 6, p e67298 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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