Genome dynamics in Legionella: the basis of versatility and adaptation to intracellular replication

Abstract

Legionella pneumophila is a bacterial pathogen present in aquatic environments that can cause a severe pneumonia called Legionnaires' disease. Soon after its recognition, it was shown that Legionella replicates inside amoeba, suggesting that bacteria replicating in environmental protozoa are able to exploit conserved signaling pathways in human phagocytic cells. Comparative, evolutionary, and functional genomics suggests that the Legionella-amoeba interaction has shaped this pathogen more than previously thought. A complex evolutionary scenario involving mobile genetic elements, type IV secretion systems, and horizontal gene transfer among Legionella, amoeba, and other organisms seems to take place. This long-lasting coevolution led to the development of very sophisticated virulence strategies and a high level of temporal and spatial fine-tuning of bacteria host-cell interactions. We will discuss current knowledge of the evolution of virulence of Legionella from a genomics perspective and propose our vision of the emergence of this human pathogen from the environment.

Figure 1.

Shared and specific gene content of eight L. pneumophila genomes. Each petal represents a genome with an associated color. The number in the center of the diagram represents the orthologous groups of genes shared by all the genomes. The number inside of each individual petal corresponds to the specific genes of each genome with nonorthologous genes in any of the other genomes. The orthologous groups were defined using the program PanOCT (Fouts et al. 2012) (the parameters used were e-value ≤1 × 10⁻⁵, percent identity ≥35, and length of the match ≥75).

Figure 2.

Phylogenetic tree of selected eukaryotic-like proteins of Legionella spp. (A) Phylogeny of the enzyme arylamine N-acetyltransferase (NAT) (Lpp2516) of L. pneumophila. (B) Phylogeny of the sphingosine-1 phosphate lyse Lpp2128 of L. pneumophila. Homolog sequences were recruited from a database containing only completed genome sequences. Selected representatives of all eukaryotic groups and one representative of each bacterial species are included in the analyses. After blastp only significant hits were recruited (e-value <10 × 10⁻⁴), and only one hit for each species was retained. The alignments were performed with T-coffee (expresso) for Lpp2616 and Muscle for Lpp2128, and followed by manual curation. Phylogenies were reconstructed using a distance method (NJ) with 1000 bootstrap replicates. The corresponding support values are shown in each node (values lower than 50 are not represented). Bars represent 20% and 10% of estimated phylogenetic divergence, respectively. (Legend continues on following page.)

Figure 2.

Phylogenetic tree of selected eukaryotic-like proteins of Legionella spp. (A) Phylogeny of the enzyme arylamine N-acetyltransferase (NAT) (Lpp2516) of L. pneumophila. (B) Phylogeny of the sphingosine-1 phosphate lyse Lpp2128 of L. pneumophila. Homolog sequences were recruited from a database containing only completed genome sequences. Selected representatives of all eukaryotic groups and one representative of each bacterial species are included in the analyses. After blastp only significant hits were recruited (e-value <10 × 10⁻⁴), and only one hit for each species was retained. The alignments were performed with T-coffee (expresso) for Lpp2616 and Muscle for Lpp2128, and followed by manual curation. Phylogenies were reconstructed using a distance method (NJ) with 1000 bootstrap replicates. The corresponding support values are shown in each node (values lower than 50 are not represented). Bars represent 20% and 10% of estimated phylogenetic divergence, respectively. (Legend continues on following page.)

Figure 3.

Model of the genetic flow inside amoeba. The accessory genome of Legionella, other intracellular bacteria, mimivirus and amoeba are contributing to a “global mobilome” that is accessible to the different organisms living inside amoeba to adapt to different conditions and allows versatility in the host–pathogen interactions.