Copper homeostasis at the host vibrio interface: lessons from intracellular vibrio transcriptomics

Abstract

Recent studies revealed that several vibrio species have evolved the capacity to survive inside host cells. However, it is still often ignored if intracellular stages are required for pathogenicity. Virulence of Vibrio tasmaniensis LGP32, a strain pathogenic for Crassostrea gigas oysters, depends on entry into hemocytes, the oyster immune cells. We investigated here the mechanisms of LGP32 intracellular survival and their consequences on the host-pathogen interaction. Entry and survival inside hemocytes were required for LGP32-driven cytolysis of hemocytes, both in vivo and in vitro. LGP32 intracellular stages showed a profound boost in metabolic activity and a major transcription of antioxidant and copper detoxification genes, as revealed by RNA sequencing. LGP32 isogenic mutants showed that resistance to oxidative stress and copper efflux are two main functions required for vibrio intracellular stages and cytotoxicity to hemocytes. Copper efflux was also essential for host colonization and virulence in vivo. Altogether, our results identify copper resistance as a major mechanism to resist killing by phagocytes, induce cytolysis of immune cells and colonize oysters. Selection of such resistance traits could arise from vibrio interactions with copper-rich environmental niches including marine invertebrates, which favour the emergence of pathogenic vibrios resistant to intraphagosomal killing across animal species.

Binding to type I collagen is essential for the infectivity ofVibrio parahaemolyticusto host cells

“…parahaemolyticus invasion (Figure ). Given that (a) increasing findings have shown that host cells entry by some Vibrio species is related to their pathogenicity (Duperthuy et al, ; Pajuelo, Lee, Roig, Hor, & Amaro, ; Rosenberg & Falkovitz, ; Vanhove et al, ), (b) MAM7 and VpadF are required for in vivo bacterial virulence (Krachler et al, ; Liu & Chen, ), and (c) type I collagen and α1β1 integrin are abundant in the small intestine (Lussier et al, ; Tulli et al, ), it is probable that the invasion of host cells is an important pathogenic process for V . parahaemolyticus .…”

Omics approaches to investigate host–pathogen interactions in mass mortality outbreaks of Crassostrea gigas

“…Furthermore, transcriptomics by RNA sequencing was investigated regarding intracellular survival mechanism of Vibrio tasmaniensis (LGP32) and its interactions with C. gigas haemocytes (Vanhove et al . ). A profound boost in metabolic activity and a major transcription of antioxidant and copper detoxification genes was observed in LGP32 intracellular stages, suggesting the key role of copper efflux and antioxidants in Vibrio survival inside host cells (Vanhove et al .…”

“…A profound boost in metabolic activity and a major transcription of antioxidant and copper detoxification genes was observed in LGP32 intracellular stages, suggesting the key role of copper efflux and antioxidants in Vibrio survival inside host cells (Vanhove et al . ).…”

Environmental vibrios: «a walk on the wild side»

“…For example virulent populations of V. tasmaniensis and V. crassostreae , have been positively associated to diseased oysters and found to co‐occur at the individual level. Infection with V. tasmaniensis involves an intracellular phase in hemocytes and resistance to antimicrobial peptides, reactive oxygen species and copper (Duperthuy et al ., , Vanhove et al ., ). Infection with V. crassostreae relies at least partially on distinct genes encoding for unknown functions (Bruto et al ., ; Lemire et al ., ).…”