Deep-sea vent epsilon-proteobacterial genomes provide insights into emergence of pathogens

Abstract

Deep-sea vents are the light-independent, highly productive ecosystems driven primarily by chemolithoautotrophic microorganisms, in particular by epsilon-Proteobacteria phylogenetically related to important pathogens. We analyzed genomes of two deep-sea vent epsilon-Proteobacteria strains, Sulfurovum sp. NBC37-1 and Nitratiruptor sp. SB155-2, which provide insights not only into their unusual niche on the seafloor, but also into the origins of virulence in their pathogenic relatives, Helicobacter and Campylobacter species. The deep-sea vent epsilon-proteobacterial genomes encode for multiple systems for respiration, sensing and responding to environment, and detoxifying heavy metals, reflecting their adaptation to the deep-sea vent environment. Although they are nonpathogenic, both deep-sea vent epsilon-Proteobacteria share many virulence genes with pathogenic epsilon-Proteobacteria, including genes for virulence factor MviN, hemolysin, invasion antigen CiaB, and the N-linked glycosylation gene cluster. In addition, some virulence determinants (such as the H(2)-uptake hydrogenase) and genomic plasticity of the pathogenic descendants appear to have roots in deep-sea vent epsilon-Proteobacteria. These provide ecological advantages for hydrothermal vent epsilon-Proteobacteria who thrive in their deep-sea habitat and are essential for both the efficient colonization and persistent infections of their pathogenic relatives. Our comparative genomic analysis suggests that there are previously unrecognized evolutionary links between important human/animal pathogens and their nonpathogenic, symbiotic, chemolithoautotrophic deep-sea relatives.

Fig. 1.

Phylogenetic tree of 16S rRNA gene sequences. The deep-sea vent ε-Proteobacteria are shown in red. Branch points conserved with bootstrap values of >75% (filled circles) and bootstrap value of 50 to 74% (open circles) are indicated. Scale bar represents the expected number of changes per position.

Fig. 2.

Central metabolism and solute transport in the deep-sea vent ε-Proteobacteria. Pathways for which no predictable enzymes were found in strains SB155-2 and NBC37-1 genomes are shown in blue and red arrows, respectively. Numbers of transport machineries are shown for both strains. The KEGG database was used for the reconstruction of metabolic pathways. Cyt, cytochrome; H₂ase, hydrogenase; Sqr, sulfide-quinone oxidoreductases; Nap, periplasmic nitrate reductase; cdNir, cytochrome cd₁ nitrite reductase; Nor, nitric oxide reductase; Nos, nitrous oxide reductase; Mdh, malate dehydrogenase; Sdh, succinate dehydrogenase.

Fig. 3.

Virulence genes in ε Proteobacteria. (A) Organization of N-linked glycosylation gene clusters. Cje, C. jejuni NCTC11168; Hpy, H. pylori 26695; Wsu, W. succinogenes DSM1740. Genes are color-coded by the function of encoded protein (essential oligosaccharyltransferase PglB, red; glycosyltransferase, yellow; enzymes involved in sugar biosynthesis, blue). Connecting lines indicate corresponding orthologs. (B) Organization of H₂-uptake and -sensing hydrogenase gene clusters. Orthologs are shown in the same colors. hydA, small subunit gene; hydB, large subunit gene; hydC, cytochrome b subunit gene; others, maturation or accessory genes necessary for the assembly of holoenzyme.

Fig. 4.

DNA-repair genes in representative Proteobacteria. Blue indicates presence, and yellow indicates absence. Hpy, H. pylori 26695; Cje, C. jejuni NCTC11168; Wsu, W. succinogenes DSM1740; Eco, Escherichia coli K12 (γ-proteobacterium); Hin, Haemophilus influenzae Rd KW20 (γ-proteobacterium); Cvi, Chromobacterium violaceum ATCC12472 (β-proteobacterium); Gsu, Geobacter sulfurreducens PCA (δ-proteobacterium).