Comparative Genomics Reveal That Host-Innate Immune Responses Influence the Clinical Prevalence of Legionella pneumophila Serogroups (original) (raw)
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Comparative Genomics Reveal That Host-Innate Immune
2013
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.
2020
Legionella pneumophila is the most common cause of the severe respiratory infection known as Legionnaires’ disease. L. pneumophila is typically a symbiont of free-living amoeba, and our understanding of the bacterial factors that determine human pathogenicity is limited. Here we carried out a population genomic study of 900 L. pneumophila isolates from human clinical and environmental samples to examine their genetic diversity, global distribution and the basis for human pathogenicity. We found that although some clones are more commonly associated with clinical infections, the capacity for human disease is representative of the breadth of species diversity. To investigate the bacterial genetic basis for human disease potential, we carried out a genome-wide association study that identified a single gene (lag-1), to be most strongly associated with clinical isolates. Molecular evolutionary analysis showed that lag-1, which encodes an O-acetyltransferase responsible for lipopolysacch...
PLOS ONE
Legionella spp. are the cause of a severe bacterial pneumonia known as Legionnaires' disease (LD). In some cases, current genetic subtyping methods cannot resolve LD outbreaks caused by common, potentially endemic L. pneumophila (Lp) sequence types (ST), which complicates laboratory investigations and environmental source attribution. In the United States (US), ST1 is the most prevalent clinical and environmental Lp sequence type. In order to characterize the ST1 population, we sequenced 289 outbreak and non-outbreak associated clinical and environmental ST1 and ST1-variant Lp strains from the US and, together with international isolate sequences, explored their genetic and geographic diversity. The ST1 population was highly conserved at the nucleotide level; 98% of core nucleotide positions were invariant and environmental isolates unassociated with human disease (n = 99) contained~65% more nucleotide diversity compared to clinical-sporadic (n = 139) or outbreak-associated (n = 28) ST1 subgroups. The accessory pangenome of environmental isolates was also~30-60% larger than other subgroups and was enriched for transposition and conjugative transfer-associated elements. Up to~10% of US ST1 genetic variation could be explained by geographic origin, but considerable genetic conservation existed among strains isolated from geographically distant states and from different decades. These findings provide new insight into the ST1 population structure and establish a foundation for interpreting genetic relationships among ST1 strains; these data may also inform future analyses for improved outbreak investigations.
BMC Genomics, 2010
Background: Discrimination between clinical and environmental strains within many bacterial species is currently underexplored. Genomic analyses have clearly shown the enormous variability in genome composition between different strains of a bacterial species. In this study we have used Legionella pneumophila, the causative agent of Legionnaire's disease, to search for genomic markers related to pathogenicity. During a large surveillance study in The Netherlands well-characterized patient-derived strains and environmental strains were collected. We have used a mixed-genome microarray to perform comparative-genome analysis of 257 strains from this collection.
2017
The city of Sydney, Australia, experienced a persistent outbreak of Legionella pneumophila serogroup 1 (Lp1) pneumonia in 2016. To elucidate the source and bring the outbreak to a close we examined the genomes of clinical and environmental Lp1 isolates recovered over 7 weeks. A total of 48 isolates from patients and cooling towers were sequenced and compared using SNP-based, core-genome MLST and pangenome approaches. All three methods confirmed phylogenetic relatedness between isolates associated with outbreaks in the Central Business District (March and May) and Suburb 1. These isolates were designated “Main cluster” and consisted of isolates from two patients from the CBD March outbreak, one patient and one tower isolate from Suburb 1 and isolates from two cooling towers and three patients from the CDB May outbreak. All main cluster isolates were sequence type ST211 which has only ever been reported in Canada. Significantly, pangenome analysis identified mobile genetic elements co...
Legionella Pneumophila Pangenome Reveals Strain-Specific Virulence Factors
BMC …, 2010
BACKGROUND: Legionella pneumophila subsp. pneumophila is a gram-negative gamma-Proteobacterium and the causative agent of Legionnaires' disease, a form of epidemic pneumonia. It has a water-related life cycle. In industrialized cities L. pneumophila is commonly encountered in refrigeration towers and water pipes. Infection is always via infected aerosols to humans. Although many efforts have been made to eradicate Legionella from buildings, it still contaminates the water systems. The town of Alcoy (Valencian Region, Spain) has had recurrent outbreaks since 1999. The strain "Alcoy 2300/99" is a particularly persistent and recurrent strain that was isolated during one of the most significant outbreaks between the years 1999-2000. RESULTS: We have sequenced the genome of the particularly persistent L. pneumophila strain Alcoy 2300/99 and have compared it with four previously sequenced strains known as Philadelphia (USA), Lens (France), Paris (France) and Corby (England).Pangenome analysis facilitated the identification of strain-specific features, as well as some that are shared by two or more strains. We identified: (1) three islands related to anti-drug resistance systems; (2) a system for transport and secretion of heavy metals; (3) three systems related to DNA transfer; (4) two CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) systems, known to provide resistance against phage infections, one similar in the Lens and Alcoy strains, and another specific to the Paris strain; and (5) seven islands of phage-related proteins, five of which seem to be strain-specific and two shared. CONCLUSIONS: The dispensable genome disclosed by the pangenomic analysis seems to be a reservoir of new traits that have mainly been acquired by horizontal gene transfer and could confer evolutionary advantages over strains lacking them.
The Genomic Sequence of the Accidental Pathogen Legionella pneumophila
Science, 2004
We present the genomic sequence of Legionella pneumophila , the bacterial agent of Legionnaires' disease, a potentially fatal pneumonia acquired from aerosolized contaminated fresh water. The genome includes a 45âkilobase pair element that can exist in chromosomal and episomal forms, selective expansions of important gene families, genes for unexpected metabolic pathways, and previously unknown candidate virulence determinants. We highlight the genes that may account for Legionella 's ability to survive in protozoa, mammalian macrophages, and inhospitable environmental niches and that may define new therapeutic targets.
Journal of Clinical Microbiology, 2014
Since the establishment of sequence-based typing as the gold standard for DNA-based typing of Legionella pneumophila, the Legionella laboratory at the Centers for Disease Control and Prevention (CDC) has conducted routine sequence-based typing (SBT) analysis of all incoming L. pneumophila serogroup 1 (Lp1) isolates to identify potential links between cases and to better understand genetic diversity and clonal expansion among L. pneumophila bacteria. Retrospective genotyping of Lp1 isolates from sporadic cases and Legionnaires' disease (LD) outbreaks deposited into the CDC reference collection since 1982 has been completed. For this study, we compared the distribution of sequence types (STs) among Lp1 isolates implicated in 26 outbreaks in the United States, 571 clinical isolates from sporadic cases of LD in the United States, and 149 environmental isolates with no known association with LD. The Lp1 isolates under study had been deposited into our collection between 1982 and 2012. We identified 17 outbreak-associated STs, 153 sporadic STs, and 49 environmental STs. We observed that Lp1 STs from outbreaks and sporadic cases are more similar to each other than either group is to environmental STs. The most frequent ST for both sporadic and environmental isolates was ST1, accounting for 25% and 49% of the total number of isolates, respectively. The STs shared by both outbreak-associated and sporadic Lp1 included ST1, ST35, ST36, ST37, and ST222. The STs most commonly found in sporadic and outbreak-associated Lp1 populations may have an increased ability to cause disease and thus may require special attention when detected.