DjlA is an inner membrane cochaperone belonging to the DnaJ family, which has been shown to be involved in Legionella sp. pathogenesis. In this study, we explored the role of this protein in the physiology and virulence of Vibrio tapetis, the etiological agent of brown ring disease (BRD) in Manila clam (Ruditapes philippinarum). Analysis of the djlA locus in V. tapetis revealed a putative organization in an operon with a downstream gene that we designated duf924 Vt , which encodes a conserved protein with an unknown function and has homologues in bacteria and eukaryotes. djlA mutants displayed a reduced growth rate and showed an important loss of cytotoxic activity against R. philippinarum hemocytes in vitro, which could be restored by extrachromosomal expression of wild-type djlA Vt but not duf924 Vt . These results are in keeping with the potential importance of DjlA for bacterial pathogenicity and open new perspectives for understanding the mechanism of action of this protein in the novel V. tapetis-R. philippinarum interaction model.Vibrio tapetis CECT4600 (formerly Vibrio Predominant 1 or VP1) was isolated in 1990 at Landeda (North Finistère, France) and was characterized as the etiological agent of brown ring disease (BRD) in the Japanese clam Ruditapes philippinarum (6, 37). BRD appeared in 1987 in Brittany (France), where this species of clam was introduced for aquaculture. Since then, the disease has been found in several marine bivalves from the United Kingdom, Ireland, Spain, Italy, and Korea (4,17,25,41). In addition, more recently, V. tapetis was isolated from the corkwing wrasse (Symphodus melops) suffering from vibriosis (22). In clams, moribund animals exhibit a brown organic deposit consisting of conchiolin, after which the disease is named, between the edge of the shell and the pallial line, and the major site of infection is the extrapallial space and the periostracal lamina (38-40). Clam sensitivity to V. tapetis seems to vary according to the geographic origin of the clams. French Manila clam populations are more susceptible to BRD than populations in the United States (1), and recently, similar findings were reported for Galician-grown Manila clams compared to Irish-grown clams (16). In addition, intraspecific molecular typing showed that there are several genetic groups that strongly correlate with the host species, suggesting that genetic modifications are responsible for host specificity (43).Like the defense strategies of many invertebrates, the clam defense strategy involves biochemical and hematological changes. Hemocytes present in the hemolymph constitute the main line of defense against infections. Infected R. philippinarum has a higher total hemocyte count and lysozyme activity, particularly in the extrapallial fluids, which are in contact with the site of infection. An increased number of granulocytes, a particular type of hemocytes with phagocytic activity, is important for the resistance of R. philippinarum to infection by V. tapetis, and severely diseased clams exhibit a decre...