0000000000009254
AUTHOR
David Pajuelo
The Effect of the Environmental Temperature on the Adaptation to Host in the Zoonotic Pathogen Vibrio vulnificus
Vibrio vulnificus is a zoonotic pathogen that lives in temperate, tropical and subtropical aquatic ecosystems whose geographical distribution is expanding due to global warming. The species is genetically variable and only the strains that belong to the zoonotic clonal-complex can cause vibriosis in both humans and fish (being its main host the eel). Interestingly, the severity of the vibriosis in the eel and the human depends largely on the water temperature (highly virulent at 28°C, avirulent at 20°C or below) and on the iron content in the blood, respectively. The objective of this work was to unravel the role of temperature in the adaptation to the host through a transcriptomic and phen…
MARTX ofVibrio vulnificusbiotype 2 is a virulence and survival factor
Vibrio vulnificus biotype 2 is a polyphyletic group whose virulence for fish relies on a plasmid. This plasmid contains an rtxA gene duplicated in the small chromosome that encodes a MARTX (Multifunctional, Autoprocessing Repeats-in-Toxin) unique within the species in domain structure (MARTX type III). To discover the role of this toxin in the fitness of this biotype in the fish-farming environment, single- and double-knockout mutants were isolated from a zoonotic strain and analysed in a series of in vivo and in vitro experiments with eel, fish cell lines and amoebae isolated from gills. Mice, murine and human cell lines were also assayed for comparative purposes. The results suggest that …
Early steps in the European eel (Anguilla anguilla)–Vibrio vulnificus interaction in the gills: Role of the RtxA13 toxin
Vibrio vulnificus is an aquatic gram-negative bacterium that causes a systemic disease in eels called warm-water vibriosis. Natural disease occurs via water born infection; bacteria attach to the gills (the main portal of entry) and spread to the internal organs through the bloodstream, provoking host death by haemorrhagic septicaemia. V.vulnificus produces a toxin called RtxA13 that hypothetically interferes with the eel immune system facilitating bacterial invasion and subsequent death by septic shock. The aim of this work was to study the early steps of warm-water vibriosis by analysing the expression of three marker mRNA transcripts related to pathogen recognition (tlr2 and tlr5) and in…
Host-Nonspecific Iron Acquisition Systems and Virulence in the Zoonotic Serovar of Vibrio vulnificus
ABSTRACT The zoonotic serovar of Vibrio vulnificus (known as biotype 2 serovar E) is the etiological agent of human and fish vibriosis. The aim of the present work was to discover the role of the vulnibactin- and hemin-dependent iron acquisition systems in the pathogenicity of this zoonotic serovar under the hypothesis that both are host-nonspecific virulence factors. To this end, we selected three genes for three outer membrane receptors ( vuuA , a receptor for ferric vulnibactin, and hupA and hutR , two hemin receptors), obtained single and multiple mutants as well as complemented strains, and tested them in a series of in vitro and in vivo assays, using eels and mice as animal models. Th…
Iron and Fur in the life cycle of the zoonotic pathogenVibrio vulnificus
Summary In this study, we aimed to analyze the global response to iron in the broad-range host pathogen Vibrio vulnificus under the hypothesis that iron is one of the main signals triggering survival mechanisms both inside and outside its hosts. To this end, we selected a strain from the main zoonotic clonal-complex, obtained a mutant in the ferric-uptake-regulator (Fur), and analyzed their transcriptomic profiles in both iron-excess and iron-poor conditions by using a strain-specific microarray platform. Among the genes differentially expressed, we identified around 250 as putatively involved in virulence and survival-related mechanisms. Then, we designed and performed a series of in vivo …
Adaptation to host inVibrio vulnificus, a zoonotic pathogen that causes septicemia in fish and humans
Vibrio vulnificus is a siderophilic pathogen spreading due to global warming. The zoonotic strains constitute a clonal-complex related to fish farms that are distributed worldwide. In this study, we applied a transcriptomic and single gene approach and discover that the zoonotic strains bypassed the iron requirement of the species thanks to the acquisition of two iron-regulated outer membrane proteins (IROMPs) involved in resistance to fish innate immunity. Both proteins have been acquired by horizontal gene transfer and are contributing to the successful spreading of this clonal-complex. We have also discovered that the zoonotic strains express a virulent phenotype in the blood of its main…
Eel immune response to Vibrio vulnificus infection. Host-pathogen relationship
The European eel (Anguilla anguilla), has experienced a dangerous decline in recruitment, yield and stock over the last 30 years and this decline is likely to continue into the future. Several major threats are responsible for this situation, including overfishing of glass eels for consumption, new infections by introduced pathogens, dams and blocking of migration routes. The lack of knowledge concerning the biology of this species represents a handicap to the conservation and recovery of the population. Nevertheless,the eel farming industry is increasing, therefore it could be considered one of the major risks for wild eel stock perpetuation, which is threatened principally by the lack of …
Novel host-specific iron acquisition system in the zoonotic pathogenVibrio vulnificus
Summary Vibrio vulnificus is a marine bacterium associated with human and fish (mainly farmed eels) diseases globally known as vibriosis. The ability to infect and overcome eel innate immunity relies on a virulence plasmid (pVvbt2) specific for biotype 2 (Bt2) strains. In the present study, we demonstrated that pVvbt2 encodes a host-specific iron acquisition system that depends on an outer membrane receptor for eel transferrin called Vep20. The inactivation of vep20 did not affect either bacterial growth in human plasma or virulence for mice, while bacterial growth in eel blood/plasma was abolished and virulence for eels was significantly impaired. Furthermore, vep20 is an iron-regulated ge…
The Fish Pathogen Vibrio vulnificus Biotype 2: Epidemiology, Phylogeny, and Virulence Factors Involved in Warm-Water Vibriosis
ABSTRACT Vibrio vulnificus biotype 2 is the etiological agent of warm-water vibriosis, a disease that affects eels and other teleosts, especially in fish farms. Biotype 2 is polyphyletic and probably emerged from aquatic bacteria by acquisition of a transferable virulence plasmid that encodes resistance to innate immunity of eels and other teleosts. Interestingly, biotype 2 comprises a zoonotic clonal complex designated as serovar E that has extended worldwide. One of the most interesting virulence factors produced by serovar E is RtxA1 3 , a multifunctional protein that acts as a lethal factor for fish, an invasion factor for mice, and a survival factor outside the host. Two practically id…