Bacterial AB toxins and host–microbe interactions

Song, Jeongmin

doi:10.1016/bs.ampbs.2022.06.002

“…In this regard, our study indicates that the glycan receptor binding PltB of ToxoidVac and PltBVac appears to effectively stimulate humoral immune responses leading to the production of typhoid toxin-neutralizing antibodies. This observation is not too surprising, as some toxoids are being used as adjuvants of human vaccines, such as tetanus toxoid for typhoid vaccine [9], while many others have also been demonstrated to be efficacious against various bacterial, viral, and parasitic pathogens [9, 36-39]. Furthermore, when the same concentrations of these two subunit vaccines were used, ToxoidVac elicited stronger humoral immune responses for anti-PltB antibodies than PltBVac (Fig.…”

Section: Discussionmentioning

confidence: 97%

The role of diets in maternal vaccinations against typhoid toxin

Neupane

¹

,

Ahn

²

,

Yang

³

et al. 2022

Preprint

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Children are particularly susceptible to typhoid fever caused by the bacterial pathogen Salmonella Typhi. Typhoid fever is prevalent in developing countries where diets can be less well-balanced. Here, using a murine model, we investigated the role of the macronutrient composition of the diet in maternal vaccination efficacies of two subunit vaccines targeting typhoid toxin: ToxoidVac and PltBVac. We found that maternal vaccinations protected all offspring against a lethal-dose typhoid toxin challenge in a balanced, normal diet (ND) condition, but the declined protection in a malnourished diet (MD) condition was observed in the PltBVac group. Despite the comparable antibody titers in both MD and ND mothers, MD offspring had a significantly lower level of typhoid toxin neutralizing antibodies than their ND counterparts. We observed a lower expression of the neonatal Fc receptor on the yolk sac of MD mothers than in ND mothers, agreeing with the observed lower antibody titers in MD offspring. Protein supplementation to MD diets, but not fat supplementation, increased FcRn expression and protected all MD offspring from the toxin challenge. Similarly, providing additional typhoid toxin-neutralizing antibodies to MD offspring was sufficient to protect all MD offspring from the toxin challenge. These results emphasize the significance of balanced/normal diets for a more effective maternal vaccination transfer to their offspring.Author summaryTyphoid fever is a life-threatening systemic infectious disease caused by Salmonella Typhi, which is prevalent in developing countries where diets can be less well-balanced. Here, we used mice to study the role of nutrition in maternal vaccination efficacies of two subunit vaccines targeting Salmonella’s typhoid toxin. We found maternal vaccinations protected all offspring from a lethal-dose typhoid toxin challenge in a balanced/normal diet (ND) condition, but the lack of protection in a malnourished diet (MD) condition was observed in the PltBVac group. Our data indicate that the difference in maternal vaccination outcomes between ND and MD offspring was due to the less effective maternal antibody transfer from MD mothers to their offspring. Providing additional proteins to MD mothers or additional toxin-neutralizing antibodies to MD offspring saved all malnourished offspring from a lethal-dose typhoid toxin challenge, highlighting the importance of balanced/normal diets for effective maternal vaccination outcomes.

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“…In this regard, our study indicates that the glycan receptor binding PltB of ToxoidVac and PltBVac appears to effectively stimulate humoral immune responses leading to the production of typhoid toxin-neutralizing antibodies. This observation is not too surprising, as some toxoids are being used as adjuvants of human vaccines, such as tetanus toxoid for typhoid vaccine [ 9 ], while many others have also been demonstrated to be efficacious against various bacterial, viral, and parasitic pathogens [ 9 , 36 – 39 ]. Furthermore, when the same concentrations of these two subunit vaccines were used, ToxoidVac elicited stronger humoral immune responses for anti-PltB antibodies than PltBVac ( Fig 1 ).…”

Section: Discussionmentioning

confidence: 99%

Malnutrition and maternal vaccination against typhoid toxin

Neupane

¹

,

Ahn²,

Yang³

et al. 2022

Self Cite

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Children are particularly susceptible to typhoid fever caused by the bacterial pathogen Salmonella Typhi. Typhoid fever is prevalent in developing countries where diets can be less well-balanced. Here, using a murine model, we investigated the role of the macronutrient composition of the diet in maternal vaccination efficacies of two subunit vaccines targeting typhoid toxin: ToxoidVac and PltBVac. We found that maternal vaccinations protected all offspring against a lethal-dose typhoid toxin challenge in a balanced, normal diet (ND) condition, but the declined protection in a malnourished diet (MD) condition was observed in the PltBVac group. Despite the comparable antibody titers in both MD and ND mothers, MD offspring had a significantly lower level of typhoid toxin neutralizing antibodies than their ND counterparts. We observed a lower expression of the neonatal Fc receptor on the yolk sac of MD mothers than in ND mothers, agreeing with the observed lower antibody titers in MD offspring. Protein supplementation to MD diets, but not fat supplementation, increased FcRn expression and protected all MD offspring from the toxin challenge. Similarly, providing additional typhoid toxin-neutralizing antibodies to MD offspring was sufficient to protect all MD offspring from the toxin challenge. These results emphasize the significance of balanced/normal diets for a more effective maternal vaccination transfer to their offspring.

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“…Many bacterial protein toxins are active through enzymatic activity and contain an enzymatic (A) domain or subunit. These toxins are referred to as AB toxins [ 29 ]. Intracellularly active toxins have additional domains, namely the translocation (T) domain, which facilitates the passage of the A domain into the cytosol, and the autoprocessing domain involved in the release of the A domain from the B domain.…”

Section: Diversity In Bacterial Protein Toxinsmentioning

confidence: 99%

“…Most of the multiprotein AB toxins retain a complex structure, for example, one A subunit and five B subunits assembled in a pentamer (AB 5 : cholera toxin (CT), shiga toxin (ST)), two distinct A subunits and five B subunits (A 2 B 5 , typhoid toxin (TyT)), one A, and two B subunits (AB 2 , cytolethal distending toxin (CDT)). Pertussis toxin (PTX) has an AB 5 structure with four distinct proteins in the B pentamer [ 29 ] ( Figure 3 ).…”

Section: Diversity In Bacterial Protein Toxinsmentioning

confidence: 99%

“…Bacterial toxins exploit cellular mechanisms to enter the target cells. Two main endocytic pathways are used: a short pathway through early endosomes (EEs) and upon endosomal acidification translocation of the A subunit into the cytosol and a long pathway including EE/late endosomes (LEs), Golgi, endoplasmic reticulum (ER), and ER secretion system such as Sec61/63 ( Figure 4 ) [ 29 , 30 ]. Most single-chain protein toxins and binary toxins deliver their enzymatic domain or enzymatic component through the endosomal membrane of acidified EEs, whereas AB 5 toxins, the B pentamer of which recognizes gangliosides or other glycoconjugates as receptors, use a long endocytic pathway through EE, LE, Golgi, and ER [ 29 ].…”

Section: Diversity In Bacterial Protein Toxinsmentioning

confidence: 99%

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Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution

Popoff

2024

Toxins

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Bacterial protein toxins are secreted by certain bacteria and are responsible for mild to severe diseases in humans and animals. They are among the most potent molecules known, which are active at very low concentrations. Bacterial protein toxins exhibit a wide diversity based on size, structure, and mode of action. Upon recognition of a cell surface receptor (protein, glycoprotein, and glycolipid), they are active either at the cell surface (signal transduction, membrane damage by pore formation, or hydrolysis of membrane compound(s)) or intracellularly. Various bacterial protein toxins have the ability to enter cells, most often using an endocytosis mechanism, and to deliver the effector domain into the cytosol, where it interacts with an intracellular target(s). According to the nature of the intracellular target(s) and type of modification, various cellular effects are induced (cell death, homeostasis modification, cytoskeleton alteration, blockade of exocytosis, etc.). The various modes of action of bacterial protein toxins are illustrated with representative examples. Insights in toxin evolution are discussed.

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Bacterial AB toxins and host–microbe interactions

Cited by 4 publications

References 148 publications

The role of diets in maternal vaccinations against typhoid toxin

The role of diets in maternal vaccinations against typhoid toxin

Malnutrition and maternal vaccination against typhoid toxin

Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution

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