Photobacterium damselae subsp. damselae, a Generalist Pathogen with Unique Virulence Factors and High Genetic Diversity

Phylogenetic relationships of the four P. damselae subsp. damselae cytotoxins with related toxins in other bacteria. (A) Damselysin (Dly) has no known homologues in any representative of the Vibrio and Photobacterium genera, thus constituting a singular feature of this subspecies. Interestingly, homologues exist in both pathogenic (A. hydrophila) and nonpathogenic (P. rubra) bacteria. (B) Phobalysin homologues are widespread in both pathogenic and environmental species of Vibrio, Photobacterium, and Aliivibrio. Also note that plasmid (PhlyP) and chromosomal (PhlyC) versions of P. damselae subsp. damselae differ in ca. 8% in their sequences and can be distinguished using a phylogenetic analysis. (C) PlpV phospholipase also has homologues in pathogenic and nonpathogenic species of the Vibrionaceae family, and it is closely related to phospholipases of the A2 type. Phylogenetic trees were constructed using the neighbor-joining method, and evolutionary distances (number of residue substitutions per site) were computed using the maximum composite likelihood method. Numbers at the tree nodes represent bootstrap values, expressed as a percentage of 1,000 replications. Accession numbers are listed in parentheses to the right of each organism name.

Diagrammatic summary of the most important features of P. damselae subsp. damselae reported to date, related to virulence and interaction with host cells. Depicted are the four main cytotoxins produced by this pathogen. PlpV phospholipase and PhlyC pore-forming toxin are encoded in chromosome I, whereas Dly sphingomyelinase and PhlyP pore-forming toxin are encoded within the pPHDD1 plasmid. The two-component regulatory system RstAB is a positive regulator of Dly, PhlyP, and PhlyC but not of PlpV. The four toxins are secreted via the type two secretion system (T2SS). It is hypothesized that, once secreted, Dly cleaves choline heads from sphingomyelin, thus allowing better access of PhlyP and PhlyC oligomers to the host cell membrane and to interaction with cholesterol molecules. PhlyP and PhlyC oligomers are thought to assemble into the host cell membrane, creating pentameric pores that cause a series of downstream effects leading to cell lysis and death. LPS, lipopolysaccharide.