The C-terminal coiled-coil domain of Corynebacterium diphtheriae DIP0733 is crucial for interaction with epithelial cells and pathogenicity in invertebrate animal model systems

Abstract

BackgroundCorynebacterium diphtheriae is the etiologic agent of diphtheria and different systemic infections. The bacterium has been classically described as an extracellular pathogen. However, a number of studies revealed its ability to invade epithelial cells, indicating a more complex pathogen-host interaction. The molecular mechanisms controlling and facilitating internalization of C. diphtheriae still remains unclear. Recently, the DIP0733 transmembrane protein was found to play an important role in the interaction with matrix proteins and cell surfaces, nematode colonization, cellular internalization and induction of cell death.ResultsIn this study, we identified a number of short linear motifs and structural elements of DIP0733 with putative importance in virulence, using bioinformatic approaches. A C-terminal coiled-coil region of the protein was considered particularly important, since it was found only in DIP0733 homologs in pathogenic Corynebacterium species but not in non-pathogenic corynebacteria. Infections of epithelial cells and transepithelial resistance assays revealed that bacteria expressing the truncated form of C. diphtheriae DIP0733 and C. glutamicum DIP0733 homolog are less virulent, while the fusion of the coiled-coil sequence to the DIP0733 homolog from C. glutamicum resulted in increased pathogenicity. These results were supported by nematode killing assays and experiments using wax moth larvae as invertebrate model systems.ConclusionsOur data indicate that the coil-coiled domain of DIP0733 is crucial for interaction with epithelial cells and pathogenicity in invertebrate animal model systems.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1247-z) contains supplementary material, which is available to authorized users.

Bone and Joint Infection Involving Corynebacterium spp.: From Clinical Features to Pathophysiological Pathways

“…Secondly, some species have been shown to produce various adhesion molecules allowing interaction with eukaryote cells. A fibrinogen and fibronectin binding-like activity has been demonstrated from invasive strains of Corynebacterium pseudodiphtericum (29), interaction with fibronectin determines corynebacteria adhesion to vaginal epithelial cells (30), and C. diphteriae can invade epithelial cells, with an important role of a transmembrane protein called DIP0733, which possesses a fibrinogen and collagen binding activity (31)(32)(33).…”

Whole genome sequence of a non-toxigenic Corynebacterium diphtheriae strain from a hospital in southeastern China

“…In addition, the DIP0733 protein could increase its ability to invade epithelial cell, as revealed by experiments in an animal model [ 23 , 24 ]. The ability of C. diphtheriae to interact with epithelial cell is mainly dependent on the C-terminal coiled-coil domain structure of DIP0733, since mutant type strains showed a decreased virulence to invertebrate animals [ 25 ]. The C-terminal sequence of GE1800 in this study was completely identical to that of DIP0733, suggesting its potential ability of infection and consequent pathogenesis.…”

Novel Insights into Phytoplasma Effectors

“…LIG_FXI_DFP_1 was found in SAP39, SAP43 and PME2; this motif is a disulfide-linked dimer, each subunit containing four apple domains (A1-4) and a C-terminal trypsin-like catalytic domain. The DFP binds to the second apple domain of coagulation factor XI and plasma kallikrein heavy chain [83]; nanobodies against factor XI apple 3 domain inhibit its protein-protein interaction, evidencing the importance of these domains [84]. These proteins are typically present in mammals and absent in plants, but coagulation factor XI and plasma kallikrein are serine proteases [85]; plant serine proteases play key roles in plant defense [86,87].…”