scholarly journals Pig vaccination strategies based on enterotoxigenic Escherichia coli toxins

Author(s):  
J. Daniel Dubreuil

AbstractEnterotoxigenic Escherichia coli (ETEC) are responsible for diarrhea in humans as well as in farm animals. ETEC infections in newborn, suckling, and especially in post-weaning piglets are associated with reduced growth rate, morbidity, and mortality. ETEC express virulence factors as adhesin and enterotoxins that play a central role in the pathogenic process. Adhesins associated with pigs are of diverse type being either fimbrial or non-fimbrial. Enterotoxins belong to two groups: heat-labile (LT) and heat-stable (ST). Heterogeneity of ETEC strains encompass expression of various fimbriae (F4, F5, F6, F18, and F41) and enterotoxins (LT, STa, STb, and EAST1). In the late years, attempts to immunize animals against neonatal and post-weaning diarrhea were focused on the development of anti-adhesin strategies as this is the initial step of ETEC pathogenesis. Although those vaccines demonstrated some protection against ETEC infections, as enterotoxins are pivotal to the virulence of ETEC, a new generation of vaccinal molecules, which include adhesin and one or more enterotoxins, were recently tested. Some of these newly developed chimeric fusion proteins are intended to control as well human diarrhea as enterotoxins are more or less common with the ones found in pigs. As these could not be tested in the natural host (human), either a mouse or pig model was substituted to evaluate the protection efficacy. For the advancement of pig vaccine, mice were sometimes used for preliminary testing. This review summarizes advances in the anti-enterotoxin immunization strategies considered in the last 10 years.

1998 ◽  
Vol 61 (2) ◽  
pp. 141-145 ◽  
Author(s):  
HAU-YANG TSEN ◽  
LIANG-ZHAO JIAN ◽  
WAN-RONG CHI

Enterotoxigenic Escherichia coli (ETEC) strains which produce heat labile and/or heat stable toxins (LT and ST) may cause diarrhea in humans and farm animals. Using PCR primers specific for the LT I and ST II genes, a multiplex PCR system which allows detection of LT I- and ST II-producing ETEC strains was developed. When skim milk was used for a PCR assay, it was found that if target cells in the sample were precultured in MacConkey broth for 8 h prior to PCR as few as 100 cells per ml of the sample could be detected. Without the preculture step, 104 CFU of target cells per 0.2 g of porcine stool specimen were required to generate visible PCR products. The multiplex PCR System can be used for rapid testing of fecal specimens, food and possibly environmental samples for the presence of ETEC strains.


Toxins ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 24 ◽  
Author(s):  
Haixiu Wang ◽  
Zifu Zhong ◽  
Yu Luo ◽  
Eric Cox ◽  
Bert Devriendt

Enterotoxigenic Escherichia coli (ETEC) are an important diarrhea-causing pathogen and are regarded as a global threat for humans and farm animals. ETEC possess several virulence factors to infect its host, including colonization factors and enterotoxins. Production of heat-stable enterotoxins (STs) by most ETEC plays an essential role in triggering diarrhea and ETEC pathogenesis. In this review, we summarize the heat-stable enterotoxins of ETEC strains from different species as well as the molecular mechanisms used by these heat-stable enterotoxins to trigger diarrhea. As recently described, intestinal epithelial cells are important modulators of the intestinal immune system. Thus, we also discuss the impact of the heat-stable enterotoxins on this role of the intestinal epithelium and how these enterotoxins might affect intestinal immune cells. Finally, the latest developments in vaccination strategies to protect against infections with ST secreting ETEC strains are discussed. This review might inform and guide future research on heat-stable enterotoxins to further unravel their molecular pathogenesis, as well as to accelerate vaccine design.


2009 ◽  
Vol 78 (1) ◽  
pp. 316-325 ◽  
Author(s):  
Weiping Zhang ◽  
Chengxian Zhang ◽  
David H. Francis ◽  
Ying Fang ◽  
David Knudsen ◽  
...  

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal disease in humans and farm animals. E. coli fimbriae, or colonization factor antigens (CFAs), and enterotoxins, including heat-labile enterotoxins (LT) and heat-stable enterotoxins (ST), are the key virulence factors in ETEC diarrhea. Unlike fimbriae or LT, STa has not often been included as an antigen in development of vaccines against ETEC diarrhea because of its poor immunogenicity. STa becomes immunogenic only after being coupled with a strongly immunogenic carrier protein. However, native or shorter STa antigens either had to retain toxic activity in order to become antigenic or elicited anti-STa antibodies that were not sufficiently protective. In this study, we genetically mutated the porcine LT (pLT) gene for a pLT192(R→G) toxoid and the porcine STa (pSTa) gene for three full-length pSTa toxoids [STa11(N→K), STa12(P→F), and STa13(A→Q)] and used the full-length pLT192 as an adjuvant to carry the pSTa toxoid for pLT192:pSTa-toxoid fusion antigens. Rabbits immunized with pLT192:pSTa12 or pLT192:pSTa13 fusion protein developed high titers of anti-LT and anti-STa antibodies. Furthermore, rabbit antiserum and antifecal antibodies were able to neutralize purified cholera toxin (CT) and STa toxin. In addition, preliminary data suggested that suckling piglets born by a sow immunized with the pLT192:pSTa13 fusion antigen were protected when challenged with an STa-positive ETEC strain. This study demonstrated that pSTa toxoids are antigenic when fused with a pLT toxoid and that the elicited anti-LT and anti-STa antibodies were protective. This fusion strategy could provide instructive information to develop effective toxoid vaccines against ETEC-associated diarrhea in animals and humans.


AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pengpeng Xia ◽  
Yunping Wu ◽  
Siqi Lian ◽  
Guomei Quan ◽  
Yiting Wang ◽  
...  

AbstractEnterotoxigenic Escherichia coli (ETEC) F4ac is a major constraint to the development of the pig industry, which is causing newborn and post-weaning piglets diarrhea. Previous studies proved that FaeG is the major fimbrial subunit of F4ac E. coli and efficient for bacterial adherence and receptor recognition. Here we show that the faeG deletion attenuates both the clinical symptoms of F4ac infection and the F4ac-induced intestinal mucosal damage in piglets. Antibody microarray analysis and the detection of mRNA expression using porcine neonatal jejunal IPEC-J2 cells also determined that the absence of FaeG subunit alleviated the F4ac promoted apoptosis in the intestinal epithelial cells. Thus, targeted depletion of FaeG is still beneficial for the prevention or treatment of F4ac infection.


1980 ◽  
Vol 29 (3) ◽  
pp. 908-913
Author(s):  
R N Greenberg ◽  
F Murad ◽  
B Chang ◽  
D C Robertson ◽  
R L Guerrant

Purified heat-stable enterotoxin (ST) from a procine strain of enterotoxigenic Escherichia coli activates quanylate cyclase in particulate fractions of rat intestinal tissue and induces fluid accumulation in suckling mice. These effects of ST were examined in the presence of either indomethacin or chlorpromazine. We also examined the effects of these two drugs on fluid accumulation in suckling mice induced by the 8-bromo analog of cyclic guanosine monophosphate. Either indomethacin or chlorpromazine reduced ST activation of guanylate cyclase. Both drugs also reduced intestinal fluid accumulation in suckling mice that resulted from submaximal doses of ST (both P < 0.001). However, there was no reduction in fluid secretion by either drug when a maximally effective dose of ST was used, suggesting that inhibition of fluid secretion by both drugs can be overcome by increasing the ST dose and that a threshold level of guanylate cyclase activity results in maximal secretory response. Both drugs also reduced basal guanylate cylase activity in rat intestinal tissue and fluid secreton in suckling mice. Chlorpromazine also reduced intestinal secretion mediated by 8-bromo cyclic guanosine monophosphate (P < 0.001). These findings indicate that chlorpromazine interferes with the effects of ST both before and after its activation of guanylate cyclase, whereas indomethacin interfers with ST only before its activation of guanylate cyclase.


Peptides ◽  
1992 ◽  
pp. 295-296
Author(s):  
Takashi Sato ◽  
Hiroshi Ozaki ◽  
Yasuo Hata ◽  
Yukiteru Katsube ◽  
Yasutsugu Shimonishi

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