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

Abstract

subsp. causes vibriosis in a variety of marine animals, including fish species of importance in aquaculture. It also may cause wound infections in humans that can progress into a fatal outcome. Two major virulence factors are encoded within the large conjugative plasmid pPHDD1: the phospholipase-D damselysin (Dly) and the pore-forming toxin Phobalysin P (PhlyP). The two toxins exert hemolytic and cytolytic activity in a synergistic manner. Albeit PhlyP has close homologues in many species, it has unique features that differentiate it from related toxins. Dly phospholipase constitutes a singular trait of subsp. among the , although related toxins are found in members of the Fish farm outbreaks can also be caused by plasmidless strains. Such observation led to the characterization of two ubiquitous, chromosome-encoded toxins with lesser cytolytic activity: the pore forming-toxin Phobalysin C (PhlyC) and the phospholipase-hemolysin PlpV. Special attention deserves the high genetic diversity of this pathogen, with a number of strain-specific features including the cell envelope polysaccharide synthesis clusters. Fish outbreaks are likely caused by multiclonal populations which contain both plasmidless and pPHDD1-harbouring isolates, and not by well-adapted clonal complexes. Still, among such a genetic heterogeneity, it is feasible to identify conserved weak points in the biology of this bacterium: the two-component regulatory system RstAB (CarSR) was found to be necessary for maximal production of virulence factors and its inactivation severely impaired virulence.

Molecular Epidemiology of Photobacterium damselae subsp. damselae Outbreaks in Marine Rainbow Trout Farms Reveals Extensive Horizontal Gene Transfer and High Genetic Diversity

“…damselae can produce a number of virulence factors to cause pathogenicity in hosts. The four main virulence factors recognized so far have cytotoxic activity for different cell types ( Osorio et al, 2018 ). Here, we found that the 31 rainbow trout strains could be divided into four distinct categories according to their haloes of β-hemolysis on sheep blood agar: a large β-hemolytic halo (LH) (7 strains), a medium halo (MH) (6 strains), a small halo (SH) (15 strains) or virtually absence of β-hemolytic halo (NH) (3 strains) ( Figure 2 ).…”

“…Previous studies have analyzed a reduced number of strains, and reported as many as 7 O-serogroups among 16 strains analyzed ( Fouz et al, 1992 ). A recent comparative analysis conducted with virulent strains of this pathogen, revealed that strains of different serogroups contain distinct gene repertories within a putative cluster for cell envelope polysaccharide synthesis ( Osorio et al, 2018 ). We therefore searched the polysaccharide synthesis homologous clusters within the genomes of strains DK2, DK3, DK20, and DK29.…”

“…The four major virulence factors investigated so far in P. damselae subsp. damselae are cytotoxins with hemolytic activity ( Osorio et al, 2018 ). Our study has confirmed that dly and hlyA pl genes, when present, always occur simultaneously, and their presence is linked to the detection of the replication origin of pPHDD1 plasmid.…”

“…Its pathogenicity is attributed to the production of up to four different toxins ( Osorio et al, 2018 ), and two main categories of strains can be distinguished. On the one side, strains harboring the virulence plasmid pPHDD1 produce the plasmid-encoded toxins damselysin (Dly) and phobalysin P (PhlyP) ( Rivas et al, 2011 ), in addition to the chromosome I-encoded toxins phobalysin C (PhlyC) and the phospholipase PlpV ( Vences et al, 2017 ).…”

“…On the other side, strains lacking pPHDD1 only produce PhlyC and PlpV. Dly is a phospholipase-D active against sphingomyelin ( Kreger et al, 1987 ) and PlpV is believed to be a phospholipase-A2 ( Osorio et al, 2018 ), whereas PhlyP and PhlyC are pore-forming toxins ( Rivas et al, 2015b ). These four toxins are secreted via the type II secretion system ( Rivas et al, 2015a ; Vences et al, 2017 ).…”