Abstract
A first strong evidence of person-to-person transmission of Legionnaires’ Disease (LD) was recently reported. Here, we characterize the genetic backbone of this case-related Legionella pneumophila strain (“PtVFX/2014”), which also caused a large outbreak of LD. PtVFX/2014 is phylogenetically divergent from the most worldwide studied outbreak-associated L. pneumophila subspecies pneumophila serogroup 1 strains. In fact, this strain is also from serogroup 1, but belongs to the L. pneumophila subspecies fraseri. Its genomic mosaic backbone reveals eight horizontally transferred regions encompassing genes, for instance, involved in lipopolysaccharide biosynthesis or encoding virulence-associated Dot/Icm type IVB secretion system (T4BSS) substrates. PtVFX/2014 also inherited a rare ~65 kb pathogenicity island carrying virulence factors and detoxifying enzymes believed to contribute to the emergence of best-fitted strains in water reservoirs and in human macrophages, as well as a inter-species transferred (from L. oakridgensis) ~37.5 kb genomic island (harboring a lvh/lvr T4ASS cluster) that had never been found intact within L. pneumophila species. PtVFX/2014 encodes another lvh/lvr cluster near to CRISPR-associated genes, which may boost L. pneumophila transition from an environmental bacterium to a human pathogen. Overall, this unique genomic make-up may impact PtVFX/2014 ability to adapt to diverse environments, and, ultimately, to be transmitted and cause human disease.
Highlights
Sequencing (WGS) is emerging as a more informative technology[18,19,20,21] since it enables an in-depth investigation of outbreak-related strains and a higher resolution power for source attribution
In 2014, Portugal hosted the second largest outbreak worldwide of Legionnaires’ disease (LD) so far, which was caused by a novel ST1905 L. pneumophila serogroup 1 strain (PtVFX/2014) likely originated from local industrial cooling towers[13]
WGS was applied to strengthen the investigation of this LD outbreak as it provides a higher level of resolution than the traditional sequence-based typing (SBT) scheme[18,19,20,21], which is based on the sequence of seven loci[16,17]
Summary
Sequencing (WGS) is emerging as a more informative technology[18,19,20,21] since it enables an in-depth investigation of outbreak-related strains and a higher resolution power for source attribution. Epidemiological, environmental, microbiological and sequence-based molecular analyses traced industrial wet cooling systems as the potential source of infection and revealed that the outbreak-related strain (here designated PtVFX/2014) was a L. pneumophila serogroup 1 displaying the novel sequence type (ST) 190513. Considering the huge genetic diversity within the L. pneumophila species[11,23,24,25,26,27], marked by the presence of key virulence traits (like the well-described Dot/Icm type IVB secretion system – T4BSS) encoded in both core- and accessory-genomes[28,29], we aimed to deeply characterize the genetic backbone of this novel person-to-person transmission- and outbreak-related strain by integrating it in the frame of the species phylogeny and diversity
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