Though attempts have been made to develop vaccines against different toxins secreted by a specific type, these can be used against a specific type of that contributes to the pathogenesis of and is believed to be produced by all the isolates [11]

Though attempts have been made to develop vaccines against different toxins secreted by a specific type, these can be used against a specific type of that contributes to the pathogenesis of and is believed to be produced by all the isolates [11]. with the WTrPFO and its nontoxic C-terminal domain name generated neutralizing antibodies, suggesting their vaccine potential against the PFO. Thus, the non-toxic C-terminal domain name of IDF-11774 PFO could serve as an alternative to PFO as a vaccine candidate. Supplementary Information The online version contains supplementary material available at 10.1007/s12026-021-09254-9. is usually a fast-growing, spore-forming, Gram-positive, rod-shaped anaerobe of the family [1, 2]. It is widely present in different habitats such as ground, food, sewage, and aquatic IDF-11774 ecosystems (marine, estuarine, and freshwater) and colonizes the gastrointestinal tract of animals and humans [3, 4]. Its ubiquitous presence in the environment is responsible for causing many histotoxic and enteric diseases in humans and animals [5]. This bacterium secretes more than 20 extracellular enzymes and toxins that are believed to be potent lethal factors behind pathogenicity [6]. Massive secretion of these toxins results in an outbreak of a broad range of diseases in animals and humans, such as gas gangrene, necrotic enteritis, food poisoning, and numerous enterotoxaemia [7, 8]Further, it is believed to be responsible for local and systemic tissue damage and the quick death of bovines [6, 9]. strains are classified into seven toxinotypes (types A, B, C, D E, F, and G) based on the production of different toxins, namely , , , ?, CPE, and NetB [10]. Perfringolysin O (PFO) is usually secreted by all the strains, and it is believed to aid other toxins of in the onset and progression of various diseases, it has not been explored for its immunogenic and vaccine potential. It has rightly been referred to as the underrated toxin due to lack of attention from the research community [15]. After exposure to without any apparent premonitory clinical indicators of necrohemorrhagic enteritis, the quick death of animals demands a safe and efficient preventive measure such as vaccination to control infections [1, 16]. In the past decades, efficient genetically designed and denatured toxoid-based vaccines have been commercially developed that could confer protective immunity to economically important livestock, including sheep, goats, and bovines, against type A after the -toxin and thus highlights the importance of PFO as a IDF-11774 potential candidate for vaccine development against [19]. The crystal structure of the PFO monomer revealed that it could be divided into four domains, domain 1 (D1), domain 2 (D2), domain 3 (D3), and domain 4 (D4) or C-terminal domain predominantly made up of -strands. Domain name 1 encompasses amino acid residues 37C53, 90C178, 229C274, and 350C373; domain name 2 encompasses IDF-11774 amino acid residues 54C89 and 374C390, and domain name 3 encompasses amino acid residues 179C228 and 275C349; thus, these are not in a continuous way. However, in the C-terminal domain name or domain name 4, the residues are continuous (391C500) [25]. The C-terminal domain name (domain name 4) is the smallest functional unit of PFO, responsible for the cholesterol acknowledgement and binding of the toxin to cholesterol-containing membranes [26, 27]. The isolated C-terminal domain was reported to be nontoxic and could identify and bind with membrane cholesterol [28]. The current study was therefore undertaken to produce soluble recombinant PFO HOXA11 using heterologous expression system and evaluate its immunogenicity in the mice model. Furthermore, since the whole toxin has been reported to be toxic to the host cell, we also assessed the immunogenicity of its receptor-binding domain name, i.e., C-terminal domain name produced using recombinant routes in parallel with WTrPFO. Further, the antisera generated against the full-length mature PFO and the C-terminal domain name was assessed for its neutralizing potential in.