Expansion, restructuring and characterization of the Legionellaceae family

Abstract

Legionellaceae is a large and widespread family of facultative intracellular bacteria with high clinical relevance. While Legionella pneumophila, the most clinically relevant species, is relatively well studied, very limited information is available regarding the other species belonging to this family, despite its only recognized genus (i.e., Legionella) being included in water regulations worldwide. Here, we analyzed publicly-available Legionellaceae isolates and metagenome-assembled genomes, nearly doubling the number of recognized species and highlighting the need to consider restructuring the familys taxonomy to include multiple genera that present distinct clinical relevance. We further found that, except for Type II and IVB secretion systems, traits linked to host invasion vary significantly across species, likely influencing their host range and survival in the environment. Presumptive genus clusters exhibited variations in metabolic capabilities, but L. pneumophila and closely related species generally displayed more complete pathways and fewer auxotrophies, suggesting a less strict intracellular lifestyle. On the contrary, specific deep-branching clades show reduced genome size and the lack of poly-3-hydroxybutyrate biosynthetic potential suggesting a stronger host association. Finally, we showed that most species are present across various environments and that, while they have apparently distinct environmental distributions, niche overlap increases at higher metabolic similarity. Together, our results shed light on the ecology of these microorganisms, highlight the diversity of traits that can occur in closely related facultative intracellular bacteria, and call for the restructuring of this family to align with genomic information and clinical relevance to aid the management of Legionellaceae bacteria. ImportanceSpecies belonging to the Legionellaceae family are responsible for Legionnaires disease, the leading waterborne disease in many industrialized countries. Historically, the focus was (and still is) on Legionella pneumophila, and the ecology of other species remained largely unknown and unexplored. However, several water safety regulations cover the entire Legionella genus,currently the only recognized within this large family, thus including species with unknown health relevance and ecology. This work provides an in-depth characterization of the genomic diversity across the family Legionellaceae, highlighting the concentration of clinically-relevant species in specific clades presenting distinct putative phenotypes linked to host invasion, metabolism and environmental niches. These findings highlight the need to consider restructuring the taxonomy of the family Legionellaceae in multiple genera to prioritize interventions to control the presence of the most clinically-relevant ones and advance public health protection.