Shiga toxin 2eB‐transgenic lettuce vaccine is effective in protecting weaned piglets from edema disease caused by Shiga toxin‐producing <i>Escherichia coli</i> infection

Hamabata, Takashi; Sato, Toshio; Takita, Eiji; Matsui, Toshimitsu; Imaoka, Taishi; Nakanishi, Nobuo; Nakayama, Katsuhiro; Tsukahara, Takamitsu; Sawada, Kazutoshi

doi:10.1111/asj.13292

Cited by 11 publications

(23 citation statements)

References 36 publications

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“…The expression cassette of 2×Stx2eB was fine-tuned to increase the accumulation of the Stx2eB protein, and the HSPT and 5′-UTR derived from Nicotiana tabacum alcohol dehydrogenase gene were used in combination with the cauliflower mosaic virus 35S RNA promoter (CaMV 35S pro.). We later confirmed that recombinant Stx2eB is functional as a vaccine (Sato et al 2013), and furthermore, three times of oral administration of approximately 1 g dry weight of freeze dried lettuce powder containing 2.3 mg Stx2eB protein relieves the pathogenic symptoms of edema disease in piglets challenged with a virulent STEC strain (Hamabata et al 2019).…”

Section: Introductionsupporting

confidence: 57%

“…If we apply the vaccine to 10% of piglets, 900,000 doses are needed. We need 6.9 mg of Stx2eB protein to protect one piglet (Hamabata et al 2019), and the accumulation level of Stx2eB in the lettuce is 6 mg per 1 g dry weight (Figure 4). We can obtain about 10 g dry weight of lettuce powder from one lettuce head with approximately 200 g fresh weight, and therefore more than 100,000 heads of lettuce is needed for 900,000 doses.…”

Section: Discussionmentioning

confidence: 99%

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Lettuce-based production of an oral vaccine against porcine edema disease for the seed lot system

Matsui

Takita

Oiwa

et al. 2021

Plant Biotechnology

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Plant-made oral vaccines can be a cost-effective method to control infectious diseases of humans and farm animals. Pig edema is a bacterial disease caused by enterohemorrhagic Escherichia coli producing the toxin Shiga toxin 2e (Stx2e). In our previous report, we chose the non-toxic B subunit of Stx2e (Stx2eB) as a vaccine antigen, and Stx2eB was expressed in lettuce (Lactuca sativa L., cv. Green wave). We found that a double repeated Stx2eB (2×Stx2eB) accumulates to higher levels than a single Stx2eB. In this study, we analyzed progeny plants introduced with 2×Stx2eB in which the gene was expressed under the control of conventional cauliflower mosaic virus 35S RNA (CaMV 35S) promoter, and found that the lettuce underwent transgene silencing and bore few seeds. We resolved these problems by using a transgene cassette which harbored a transcriptional promoter derived from the lettuce ubiquitin gene and a longer version of HSPT. The lettuce harboring this expression construct will be valuable in establishing the seed lot system on the basis that thousands of seeds can be obtained from one plant body and the resulting progeny plants accumulate 2×Stx2eB at high levels without the transgene silencing.

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Section: Introductionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Lettuce-based production of an oral vaccine against porcine edema disease for the seed lot system

Matsui

Takita

Oiwa

et al. 2021

Plant Biotechnology

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“…This data agrees with results from a study by Brand et al ( 40 ) that found a high level of AMR, in particular to tetracycline (50%), sulfamethoxazole (49%), trimethoprim (34%), and ampicillin (26%) in E. coli isolates from pigs. These results and the increasing awareness on drug-resistant E. coli strains, related to the prophylactic use of antibiotics on healthy piglets or as food additive ( 60 ), highlight the need to develop a vaccine against Stx2e-producing isolates as an useful method alternatively to antimicrobials ( 61 ). In addition, an effective vaccine program is desirable in order to prime immunity able to confirm protection to the effect of toxins ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Pathogenicity of Shiga Toxin Type 2e Escherichia coli in Pig Colibacillosis

et al. 2020

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Shiga toxin type 2e (Stx2e) Escherichia coli is the causative factor of diarrhea and edema in swine. The aims of this study were to determine the prevalence of Stx2e-producing E. coli isolates and to characterize isolates from clinical cases of pig colibacillosis and healthy swine. During the 11 years of the study (2006-2017), a total of 233 Stx2e-producing isolates were detected−230 out of 2,060 (11.16%) E. coli isolated from diseased pigs and 3 out of 171 (1.75%) from healthy swine. Stx2e-producing isolates were indeed more present in clinical colibacillosis cases than in healthy pigs (p = 0.0002). The predominant serogroup was O139 (79.82%) and the most common fimbrial factor present in these isolates was F18 (177 isolates), followed by F6 (5 isolates). The enterotoxins LTI, STa, and STb were detected in 10.43, 41.73, and 48.26% of the isolates, respectively. The predominant virotypes F18-Stx2e and-STa-STb-Stx2e were similarly present in weaners (33.33 and 35.52%) and finishers (38.30 and 25.53%). Among isolates from diseased pigs, O139 and F18 were the more frequently identified serogroup and virulence factor, respectively. Of the tested 230 Stx2e-producing isolates isolated from diseased pigs, 29 (12.60%) harbored genes encoding ESBL, particularly TEM (79.30%), CTX-M1 (17.20%), and CMY-2 (3.40%). Antimicrobial resistance to tetracycline was the most common characteristic (98.25%), followed by ampicillin (93.91%), cephalotin (90.43%) and trimethoprim/sulfamethoxazole (82.17%). Our results showed that Stx2e-producing E. coli were more frequently associated with clinical forms of colibacillosis, with minimal probability to isolate these isolates from healthy pigs.

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“…For the treatment of porcine edema disease, which is a severe and often fatal disease in pigs that is also mediated by Stx (in this case subtype Stx2e), Hamabata et al have recently developed stx2eB-transgenic lettuce for immunization. Infection of piglets with STEC after oral vaccination by feeding the lettuce showed decreased levels of pathogenesis in lettuce-fed piglets (Hamabata et al, 2019).…”

Section: Toxin-targeted Plant-based Vaccinesmentioning

confidence: 94%

Treatment Strategies for Infections With Shiga Toxin-Producing Escherichia coli

Mühlen

Dersch

2020

Front. Cell. Infect. Microbiol.

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Infections with Shiga toxin-producing Escherichia coli (STEC) cause outbreaks of severe diarrheal disease in children and the elderly around the world. The severe complications associated with toxin production and release range from bloody diarrhea and hemorrhagic colitis to hemolytic-uremic syndrome, kidney failure, and neurological issues. As the use of antibiotics for treatment of the infection has long been controversial due to reports that antibiotics may increase the production of Shiga toxin, the recommended therapy today is mainly supportive. In recent years, a variety of alternative treatment approaches such as monoclonal antibodies or antisera directed against Shiga toxin, toxin receptor analogs, and several vaccination strategies have been developed and evaluated in vitro and in animal models. A few strategies have progressed to the clinical trial phase. Here, we review the current understanding of and the progress made in the development of treatment options against STEC infections and discuss their potential.

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Shiga toxin 2eB‐transgenic lettuce vaccine is effective in protecting weaned piglets from edema disease caused by Shiga toxin‐producing Escherichia coli infection

Cited by 11 publications

References 36 publications

Lettuce-based production of an oral vaccine against porcine edema disease for the seed lot system

Lettuce-based production of an oral vaccine against porcine edema disease for the seed lot system

Pathogenicity of Shiga Toxin Type 2e Escherichia coli in Pig Colibacillosis

Treatment Strategies for Infections With Shiga Toxin-Producing Escherichia coli

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