Characterization and Attenuation of Regulatory Network of Vibrio vulnificus RtxA Encoding a MARTX Toxin
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Single Donor Human Red Blood Cells from Innovative Research was used in the following study:
Zee-Won Lee
Department of Agricultural Biotechnology, Seoul National University
August 2020
Vibrio vulnificus is a gram-negative bacterium in the Vibrio genus in Vibrionaceae. Unlike other members of the Vibrio genus, V. vulnificus can ferment lactose. The bacterium inhabits predominantly marine environments around the world and has been reported to adapt to survive in a wide range of water temperatures and salinity concentrations. V. vulnificus can naturally exist independently or be associated with zooplankton and other such marine organisms. When V. vulnificus is taken up by filter-feeding mollusks of fish species that feed on mollusks of plankton the virus becomes concentrated in their gut and other tissues. This results in these marine organisms serving as an environmental reservoir for the transmission of V. vulnificus.
V. vulnificus is an opportunistic human pathogen capable of causing serious, even fatal, foodborne illnesses when consumed in the form of infected seafood. Additionally, V. vulnificus infection may also result from exposing open wound to water containing the pathogen during recreational activities such as swimming or fishing, or even by simply handling infected seafood.
Though there are many factors that influence the virulence of V. vulnificus, a multifunctional-autoprocessing repeats-in-toxin (MARTX) toxin rtxA plays an essential role. This study examined additional regulatory proteins, along with various environmental signals, involved in rtxA expression. As a result, a leucine-responsive regulatory protein (Lrp) was found to be a positive regulator of rtxA. Further testing revealed that Lrp activates the rtxA expression by binding directly and specifically to PrtxA. Taken together, a regulatory network coordinates the expression of rtxA in response to changes in the host environment. Through high throughput screening a small molecule was identified as an inhibitor and named CM14. CM14 reduces HlyU-dependent virulence gene expression in V. vulnificus without suppressing the bacterial growth or causing host cell death.
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