Putting antimicrobial resistance in the corner

Authors: Li, Charles; LU, MINGMIN - US Department Of Agriculture (USDA)

Submitted to: Nature Food
Publication Type: Review Article
Publication Acceptance Date: 2/8/2020
Publication Date: 2/10/2020
Citation: Li, C.Z., Lu, M. 2020. Putting antimicrobial resistance in the corner. Nature Food. https://doi.org/10.1038/s43016-020-0034-9.
DOI: https://doi.org/10.1038/s43016-020-0034-9

Interpretive Summary: Invited commentary article: Antibiotics as growth promoters (AGP) have been used in the practice of food animal production for decades, and have effectively promoted animal production and inhibited the animal diseases for decades. However, abuse of antibiotics has resulted in the concerns over environmental pollutions, food safety and human health due to antibiotic residuals present in the meat products, and broad emergence of antimicrobial resistance pathogens. Pathogens, especially the Gram-negative bacteria, are very smartly evolving to develop the antibiotic resistance through a diversity of complex molecular mechanism. As more countries began to ban the antibiotics as feed additives, rising incidences of enteric infectious diseases were found to be associated with this trend of increased legislative restrictions and the voluntary withdrawals of AGP use worldwide. Therefore, there is a critical need to develop innovative antimicrobials that provide alternatives to conventional antibiotics. Coccidiosis is a major protozoan parasitic disease negatively impact poultry feed intake, low weight gain and production of reared chickens. With the occurrence of drug resistance for the primary ionophore antibiotic as anticoccidial drugs and vaccine concerns, antibiotic alternative approaches need to be further explored for coccidiosis control. Eimerial infection induces excess local production of intestine luminal IL-10 which suppresses the immune responses to facilitate the coccidiosis disease progression. Lessard and co-authors in this issue of Nature Food now present an alternative approach to mitigate the coccidiosis severity through feeding the chickens with transgenic corn expressing antibody specific for chicken interleukin-10 (cIL-10). corn. The authors developed a single domain antibody (AgThG11) binding to cIL-10, and expressed the recombinant proteins in transgenic corn. The chickens fed the transgenic corn had improved body weight gain, normalized feed conversion ratio, reduced oocyst counts below the infected untreated control animals following challenge with multiple Eimeria spp. The expressed antibody derived from their transgenic corn was able to bind the cIL-10 in vitro, block cIL-10 receptor binding efficiently. The microbially produced AgThG11 had a trait of great thermal stability (retaining 50% of binding affinity of the antibody to cIL-10 at 95 0C for 3 min, and 15% at 95 0C for 30 min). In addition, there recombinant antibodies demonstrated high concentration in transgenic corn (0.87 mg per gram of corn) for a simple processing by feed pelleting to feed chickens. Overall, the AgThG11 antibody expressed in transgenic corn allowed the robustness for farm use in pellet feed without extra requirements of complicated and costly antibody harvesting, purification and formulation steps, making it attractive for poultry-raising farmers in the developing countries. Future work should be determined if the transgenic corn expressing antibody specific for cIL-10 would show the similar growth enhancement and lesion mitigation effects for other pathogen-infections in animals, especially in the poultry.

Technical Abstract: Invited commentary article: Antibiotics as growth promoters (AGP) have been used in the practice of food animal production for decades, and have effectively promoted animal production and inhibited the animal diseases for decades. However, abuse of antibiotics has resulted in the concerns over environmental pollutions, food safety and human health due to antibiotic residuals present in the meat products, and broad emergence of antimicrobial resistance pathogens. Pathogens, especially the Gram-negative bacteria, are very smartly evolving to develop the antibiotic resistance through a diversity of complex molecular mechanism. As more countries began to ban the antibiotics as feed additives, rising incidences of enteric infectious diseases were found to be associated with this trend of increased legislative restrictions and the voluntary withdrawals of AGP use worldwide. Therefore, there is a critical need to develop innovative antimicrobials that provide alternatives to conventional antibiotics. Coccidiosis is a major protozoan parasitic disease negatively impact poultry feed intake, low weight gain and production of reared chickens. With the occurrence of drug resistance for the primary ionophore antibiotic as anticoccidial drugs and vaccine concerns, antibiotic alternative approaches need to be further explored for coccidiosis control. Eimerial infection induces excess local production of intestine luminal IL-10 which suppresses the immune responses to facilitate the coccidiosis disease progression. Lessard and co-authors in this issue of Nature Food now present an alternative approach to mitigate the coccidiosis severity through feeding the chickens with transgenic corn expressing antibody specific for chicken interleukin-10 (cIL-10). corn. The authors developed a single domain antibody (AgThG11) binding to cIL-10, and expressed the recombinant proteins in transgenic corn. The chickens fed the transgenic corn had improved body weight gain, normalized feed conversion ratio, reduced oocyst counts below the infected untreated control animals following challenge with multiple Eimeria spp. The expressed antibody derived from their transgenic corn was able to bind the cIL-10 in vitro, block cIL-10 receptor binding efficiently. The microbially produced AgThG11 had a trait of great thermal stability (retaining 50% of binding affinity of the antibody to cIL-10 at 95 0C for 3 min, and 15% at 95 0C for 30 min). In addition, there recombinant antibodies demonstrated high concentration in transgenic corn (0.87 mg per gram of corn) for a simple processing by feed pelleting to feed chickens. Overall, the AgThG11 antibody expressed in transgenic corn allowed the robustness for farm use in pellet feed without extra requirements of complicated and costly antibody harvesting, purification and formulation steps, making it attractive for poultry-raising farmers in the developing countries. Future work should be determined if the transgenic corn expressing antibody specific for cIL-10 would show the similar growth enhancement and lesion mitigation effects for other pathogen-infections in animals, especially in the poultry.