Variable Virulence of Biotype 3 Vibrio vulnificus due to MARTX Toxin Effector Domain Composition

Abstract

Vibrio vulnificus is a serious infection linked to climate change. The virulence capacity of these bacteria can vary by gene exchange, resulting in new variants of the primary virulence toxin. In this study, we tested whether the emergence of an epidemic strain of V. vulnificus with a novel toxin variant correlated with a change in virulence. We found that restoring the biotype 3 toxin variant to the putative progenitor-type toxin resulted in dramatically increased virulence, revealing that the emergence of the biotype 3 strain could be linked to virulence reduction. This reduced virulence, previously found also in the biotype 1 strain, suggests that reduced virulence may stimulate outbreaks, as strains have greater capacity to enter the human food chain through reduced impact to environmental hosts.

Coordinated delivery and function of bacterial MARTX toxin effectors

“…Notably, removal of the RRSP domain that cleaves Ras dramatically reduces virulence of V. vulnificus strain CMCP6, while removal of MCF did not dramatically affect virulence (Kwak et al, 2011;Gavin and Satchell, 2017). By contrast, completely swapping MCF and RRSP in place of ExoY and DmX in the BT3 V. vulnificus strain to match its putative progenitor strain dramatically increased virulence (Kim et al, 2017). Finally, a recent study found that the collection of certain effector domains could induce the expression of pro-inflammatory genes, while another strain with a different set of effectors can downregulate many pro-inflammatory genes (Murciano et al, 2017).…”

“…3). Indeed, effector 'crosstalk' may contribute to why bacterial strains with different effector combinations have differences in virulence (Kwak et al, 2011;Kim et al, 2017;Murciano et al, 2017). Effector crosstalk has already been directly demonstrated in the MARTX toxin of V. cholerae.…”

“…Additionally, as more is discovered about the function of the effector domains, future work will have to delve into how these effectors function together to promote virulence. As observed in V. vulnificus, strains containing different MARTX toxin effector repertories have different virulence potential (Kwak et al, 2011;Kim et al, 2017;Murciano et al, 2017). While this could be the result of each effector having different effects on cell function or gene expression with the holotoxin adding up by the sum of its parts, it may not be that simple.…”

How Should I Submit to mSphere : Traditional, Expedited, or mSphereDirect?

“…In addition, we have uploaded what we believe to be a great example of how the process should take place ( http://msphere.asm.org/sites/default/files/additional-assets/mSDSample.pdf ). We are grateful to Karla Satchell and her coauthors, as well as to Carmen Amaro and Jonathon Audia, the external solicited reviewers, for doing such a wonderful job and for graciously allowing us to post their documents relating to the Satchell laboratory’s report on Vibrio vulnificus virulence ( 2 ).…”

Accessory Toxins of Vibrio Pathogens and Their Role in Epithelial Disruption During Infection

“…Although it is not its primary pathology, V vulnificus is capable of producing gastroenteritis among its clinical manifestations. This pathogen secretes a number of exotoxins and enzymes ( Liu et al, 2007 ), among which the cytolysin VvhA ( Kim et al, 2017 ) and metalloprotease Vvp ( Lee et al, 2008 ; Chen et al, 2017 ) are the most important join to RTX. This last toxin has been strongly associated with the virulence of this organism ( Lee et al, 2007 , 2008 ).…”