The auxotrophic aroA mutant of Aeromonas hydrophila as a live attenuated vaccine against A. salmonicida infections in rainbow trout (Oncorhynchus mykiss)

Vivas, J.; Riaño, Jorge; Carracedo, Begoña; Razquin, B.; López‐Fierro, P.; Naharro, Germán; Villena, A.

doi:10.1016/s1050-4648(03)00078-0

Cited by 50 publications

(41 citation statements)

References 34 publications

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“…Our study reveals the effect of the aroA mutation on the behavior of the A. hydrophila live vaccine in freshwater at temperatures (16 to 20°C) at which the efficacy of this vaccine has been tested (74) and that are similar to those at which vaccination in fish farms is usually carried out (38) or at a temperature that can be found in salmonid rivers (6°C).…”

Section: Discussionmentioning

confidence: 87%

“…This effect may be explained by the fact that 20°C is closer to the optimal growth temperature of the bacteria. Therefore, attenuation of the live vaccine, which is related to the decreased ability of the bacteria to persist in host tissues (25,74), may also modulate survival in water. Other authors have reported that mutations in strains used as live vaccines may have consequences for resistance to various environmental stresses (17,62).…”

Section: Discussionmentioning

confidence: 99%

“…This culture medium was selected for the survival studies because it allows the easy growth of Aeromonas species (5) and, in particular, aroA cells grown in TSB provided significant protection in vaccination-challenge studies with trout (25,74). Inocula were prepared from cells harvested from earlier (14-h) and later (24-h) stationary-growth-phase cultures.…”

Section: Methodsmentioning

confidence: 99%

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Behavior of an Aeromonas hydrophila aroA Live Vaccine in Water Microcosms

Vivas¹,

Carracedo²,

Riaño³

et al. 2004

Appl Environ Microbiol

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Genetically modified auxotrophic mutants of different fish pathogens have been used as live vaccines in laboratory experiments, but the behavior of the strains after release into aquatic ecosystems has not been characterized. We previously constructed and characterized an aroA mutant of Aeromonas hydrophila and studied the protection afforded by this mutant as a live vaccine in rainbow trout. In this work, we describe the survival of this strain in aquatic microcosms prepared from fish water tanks. The aroA mutant disappeared rapidly in nonfiltered, nonautoclaved fish tank water, declining below detection levels after 15 days, suggesting an inhibitory effect of the autochthonous microflora of the water. When the aroA strain was used to inoculate sterilized water, its culturability was lower than that of wild-type strain A. hydrophila AG2; after long periods of incubation, aroA cells were able to enter a viable but nonculturable state. Entry into this nonculturable state was accompanied by changes in the cell morphology from rods to spheres, but the cells appeared to remain potentially viable, as assessed by the preservation of cell membrane integrity. Supplementation of the culture medium with sodium pyruvate favored the culturability and resuscitation of the two A. hydrophila strains at low temperatures (6 and 16°C). These results contribute to a better understanding of the behavior of the aroA strain in natural environments and suggest that the inactivation of the aroA gene may be beneficial for the safety of this live vaccine for aquacultures.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Behavior of an Aeromonas hydrophila aroA Live Vaccine in Water Microcosms

Vivas¹,

Carracedo²,

Riaño³

et al. 2004

Appl Environ Microbiol

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“…We chose two different mutagenesis targets: aromatic amino acid metabolism and the QS system. Auxotrophic strains (notably auxotrophic for aromatic amino acids) have been generated to obtain attenuated vaccine strains in mammals (1,4,10) and fish (26) to trigger a protective antibacterial response and in immunotherapy studies to obtain safer vectors (16). Our ⌬aroA mutants (CHA-OA and CHA-OAL) have reduced growth rates in LB and VB media, and the dramatic mortality reduction observed when injecting high amounts of these strains into C57BL/6 mice is likely to be related to a low multiplication in the host, allowing elimination of the bacteria.…”

Section: Discussionmentioning

confidence: 99%

Optimization of a Type III Secretion System-Based Pseudomonas aeruginosa Live Vector for Antigen Delivery

Épaulard

Derouazi

Margerit

et al. 2008

Clin Vaccine Immunol

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During the last few years, the use of type III secretion system-based bacterial vectors for immunotherapy purposes has been assessed in various applications. We showed that a type III secretion-based Pseudomonas aeruginosa vector delivering the ovalbumin (OVA) antigen induced an efficient specific CD8 ؉ T-lymphocyte immune response against OVA-expressing cells. Because of the intrinsic toxicity of the vector, further virulence attenuation was needed. Therefore, we explored the effects of the deletion of quorum-sensing genes and the aroA gene toward toxicity and efficiency of the vector strain. The aroA mutation in our strain (making the strain auxotrophic for aromatic amino acids) conferred a strikingly reduced toxicity, with the bacterial lethal dose being more than 100 times higher than that of the parental strain. The quorum-sensing gene mutation alone was associated with a slightly reduced toxicity. In a prophylactic OVA-expressing melanoma mouse model, an OVA-delivering aroA-deficient mutant was the most efficient at a low dose (10 5 ), but dose enhancement was not associated with a greater immune response. The quorum-sensing-deficient strain was the most efficient at a mild dose (10 6 ), but this dose was close to the toxic dose. Combination of both mutations conferred the highest efficiency at an elevated dose (10 7 ), in agreement with the known negative effects of quorum-sensing molecules upon T-cell activation. In conclusion, we have obtained a promising immunotherapy vector regarding toxicity and efficiency for further developments in both antitumor and anti-infectious strategies.The use of live bacteria and bacterial virulence factors as therapeutic tools in human medicine has been considered for more than a century. The observation that the onset of a bacterial infection could modify the course of a malignant disease (6) was a hallmark in this history, but in the end very few procedures (such as the intravesical administration of an attenuated Mycobacterium bovis strain for the cure of noninvasive urothelial carcinoma) have been routinely used. In the last 10 years, better characterization of bacterial mechanisms (mainly toxins and secretion systems) and extensive progress in genomic studies have allowed engineering of bacteria (mainly Escherichia coli and Salmonella spp.). These domesticated agents can be delivered to mammals for different purposes. Notably, the design of antigen-delivering bacteria that trigger antigen-specific cytotoxic CD8 ϩ T-lymphocyte responses is an emerging field of investigation in vaccine development (5). Antigen delivery can be performed by using intrinsic properties of bacterial toxins (as with a Listeria monocytogenes-derived vector [21]) or secretion pathways normally used by bacteria to release toxins, such as the type III secretion system (TTSS). This system has been considered promising because it allows gram-negative rods to inject toxins into eukaryotic cell cytoplasm; therefore, epitopes delivered by this system are likely to be presented by antigen-presenting c...

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“…including whole cell, outer membrane proteins, extra-cellular proteins, lipopolysaccharides, biofilms and live aeroA mutant attenuated vaccines [13,15]. While each medicine probably are effective in the treatment of a particular disease, problems arise with the development of possible pathological side effects of immunization in fishes, as well as the emergence of antibiotic resistant pathogenic strains.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress biomarkers in gills of brown trout (Salmo trutta m. fario) vaccinated against furunculosis

Tkachenko¹,

Grudniewska²

2015

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The auxotrophic aroA mutant of Aeromonas hydrophila as a live attenuated vaccine against A. salmonicida infections in rainbow trout (Oncorhynchus mykiss)

Cited by 50 publications

References 34 publications

Behavior of an Aeromonas hydrophila aroA Live Vaccine in Water Microcosms

Behavior of an Aeromonas hydrophila aroA Live Vaccine in Water Microcosms

Optimization of a Type III Secretion System-Based Pseudomonas aeruginosa Live Vector for Antigen Delivery

Oxidative stress biomarkers in gills of brown trout (Salmo trutta m. fario) vaccinated against furunculosis

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