Seeding and Establishment of Legionella pneumophila in Hospitals: Implications for Genomic Investigations of Nosocomial Legionnaires’ Disease

Abstract

SummaryWhole-genome sequencing can be used to support or refute suspected links between hospital water systems and Legionnaires’ disease cases. However, caveats regarding the interpretation of genomic data from Legionella pneumophila are described that should be considered in future investigations.

A supervised statistical learning approach for accurateLegionella pneumophilasource attribution during outbreaks

“…From a biological perspective, the lack of genetic diversity in Lpn-SG1 over such coarse temporal and spatial scales is potentially explained by a reservoir of latent-state bacteria intermittently seeding warm water sources in the greater Melbourne region and is supported by the frequently-reported and widespread presence of Legionella species in drinking water supply systems (DWSS) (32-34). Independent studies propose similar hypotheses to explain the surprisingly high sequence conservation among some L. pneumophila genomes (8, 12).…”

“…In order to appraise the utility of this method beyond a large urban setting and the ST30 genotype, we built a sister model using 31 ST1 environmental L. pneumophila genomes from a previously published hospital investigation in Essex, UK, and used it to predict the origins of seven nosocomial clinical isolates (Fig. 3A, Table S1) (8). Here, the model was trained using an alignment of 59 non-recombinogenic SNPs among the 31 environmental genomes and retaining the first 15 PCs, as this was found to be optimal.…”

“…Again, a single discrepancy occurred with a ward G genome predicted to originate from ward A. Wards A and G were co-located on the same corner and level of a common building, again suggesting a common L. pneumophila source (8). As before, isolates from a common source would be miss-assigned by the model, owing to the lack of location-specific genomic variants.…”

“…Increasingly, whole genome sequencing (WGS) is being employed to investigate individual Legionella outbreaks and the insights obtained from these high-resolution comparisons are challenging our expectations regarding common-source outbreaks, which usually are characterized by a single strain or genotype (5-9). It is becoming evident that outbreaks can be caused by multiple co-circulating L. pneumophila genotypes (5, 10) and that L. pneumophila core genomes can be surprisingly conserved across space and time (8, 11-13).…”

“…This collection included 11 clinical and 14 environmental isolates from the Aquarium outbreak and 42 clinical and 50 environmental isolates from 28 other likely point source case clusters. We also assessed genomic data from a recently described investigation of Legionnaires’ cases at a UK hospital (8). The aim of this project was to develop a robust genomic approach that would surmount the unusual population structure of L. pneumophila and assist identification of case clusters and source tracking efforts during Legionnaires’ disease outbreak investigations.…”