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.

The Legionella pneumophila Collagen-Like Protein Mediates Sedimentation, Autoaggregation, and Pathogen-Phagocyte Interactions

“…All the tested isolates were capable of sedimentation, with the exception of L. pneumophila serogroup 3 and L. pneumophila serogroup 8, which showed only a moderate aggregation (Fig. 1B) and which have a low clinical prevalence (9,40). Although most serogroups are able to autoaggregate, this suggests that differences in O-antigen decoration may have an impact on the aggregation of L. pneumophila, consistent with the effect of O-antigen differences on E. coli autoaggregation (9).…”

Epidemiological Investigation of Legionella pneumophila Serogroup 2 to 14 Isolates from Water Samples by Amplified Fragment Length Polymorphism and Sequence-Based Typing and Detection of Virulence Traits

“…Specific genetic loci lvh and rtxA were chosen because they were suggested as appropriate indicators of L. pneumophila virulence after 19 major virulence genes were studied (42). A genetic element of the lvh locus in the genome of strain Philadelphia 1 (derived from the strain of the first outbreak in Philadelphia, PA) was detected in the genome of an Lp6 strain that has been sequenced in Canada (43). Different studies suggest that there is recombination and horizontal gene transfer through the plasmid pP36 of the lvh locus and other loci involved in type IV secretion systems (43,44).…”

“…A genetic element of the lvh locus in the genome of strain Philadelphia 1 (derived from the strain of the first outbreak in Philadelphia, PA) was detected in the genome of an Lp6 strain that has been sequenced in Canada (43). Different studies suggest that there is recombination and horizontal gene transfer through the plasmid pP36 of the lvh locus and other loci involved in type IV secretion systems (43,44). rtxA encodes the dot/icm-regulated pore-forming toxin and plays a significant role in the entry of the bacteria into the host cell (17).…”

Legionella species diversity and dynamics from surface reservoir to tap water: from cold adaptation to thermophily

“…Only a restricted set of genotypes of L. pneumophila is virulent and able to cause disease (Sobral et al, 2011;Khan et al, 2013;Phin et al, 2014). On the other hand, DWSS can be considered as highly diverse ecosystems providing a wealth of niches for selection and potentially adaptation or even evolution of specific genotypes as shown by the genotype pattern in large and small water supply systems (Sobral et al, 2011;Khan et al, 2013;Rodríguez-Martínez et al, 2015).…”