Abstract
RtxA1 is a major cytotoxin of Vibrio vulnificus (V. vulnificus) causing fatal septicemia and necrotic wound infections. Our previous work has shown that RpoS regulates the expression and secretion of V. vulnificus RtxA1 toxin. This study was conducted to further investigate the potential mechanisms of RpoS on RtxA1 secretion. First, V. vulnificus TolCV1 and TolCV2 proteins, two Escherichia coli TolC homologs, were measured at various time points by Western blotting. The expression of TolCV1 was increased time-dependently, whereas that of TolCV2 was decreased. Expression of both TolCV1 and TolCV2 was significantly downregulated in an rpoS deletion mutation. Subsequently, we explored the roles of TolCV1 and TolCV2 in V. vulnificus pathogenesis. Western blot analysis showed that RtxA1 toxin was exported by TolCV1, not TolCV2, which was consistent with the cytotoxicity results. Furthermore, the expression of TolCV1 and TolCV2 was increased after treatment of the host signal bile salt and the growth of tolCV1 mutant was totally abolished in the presence of bile salt. A tolCV1 mutation resulted in significant reduction of V. vulnificus induced-virulence in mice. Taken together, TolCV1 plays key roles in RtxA1 secretion, bile salt resistance, and mice lethality of V. vulnificus, suggesting that TolCV1 could be an attractive target for the design of new medicines to treat V. vulnificus infections.
Highlights
Vibrio vulnificus (V. vulnificus) is a halophilic Gram-negative bacterium that causes fatal primary septicemia and necrotizing wound infections, and is commonly transmitted by seawater exposure or contaminated seafood consumption (Baker-Austin et al, 2018; Park and Lee, 2018)
Results showed that both TolCV1 and TolCV2 expression levels in the rpoS mutant strain were significantly lower than those in the wild-type (Figure 1B), indicating that RpoS acts as a positive regulator in TolCV1 and TolCV2 expressions
We concluded that the regulatory effect of RpoS on RtxA1 secretion was achieved by regulating the expression of TolCV1
Summary
Vibrio vulnificus (V. vulnificus) is a halophilic Gram-negative bacterium that causes fatal primary septicemia and necrotizing wound infections, and is commonly transmitted by seawater exposure or contaminated seafood consumption (Baker-Austin et al, 2018; Park and Lee, 2018). Our previous studies have demonstrated that the expression of RtxA1 is dramatically increased after the close contact of V. vulnificus with host cells (Kim et al, 2008), and RtxA1 toxin induces the acute cell death by forming pores in the cellular membrane (Kim et al, 2013). V. vulnificus TolC, an outer membrane channel protein that participates in the assembly of tripartite efflux pumps, has been reported to be involved in the secretion of RtxA1 toxin (Hwang et al, 2011). In V. vulnificus, there are two Escherichia coli (E.coli) TolC homologs, TolCV1 and Vibrio vulnificus TolC Proteins
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
