SBIR Phase I: New antibiotic technologies to eliminate Salmonella carriage in poultry

这一小型企业创新研究(SBIR)项目的更广泛影响/商业潜力是开发减少家禽中致病性沙门氏菌携带的技术。应对的挑战是食源性细菌性胃肠道感染。这些感染是全世界发病率和死亡率的重要原因。令人担忧的是出现了对抗生素具有抗药性的细菌。耐药性发展的一个主要来源是抗生素在动物生产中的广泛使用。据估计，美国生产的所有抗生素中有70%用于家畜，主要是为了促进生长和提高饲料效率，即使在没有感染的情况下也是如此。这种对动物的亚治疗性抗生素给药为选择抗药性细菌创造了一个巨大的蓄水池。作为这一问题的潜在解决方案，益生菌将被改造成在动物的胃肠道(GI)中表达和分泌抗菌肽(AMPs)的工程菌。在这项应用中，重点放在鸡上，这是全球饮食中动物蛋白的重要来源。在美国，食源性沙门氏菌每年感染数百万人，而沙门氏菌中毒的主要来源是家禽产品。目标是减少鸡只携带沙门氏菌，以确保食品安全和减少对抗生素的需求。这个小型企业创新研究第一阶段项目将评估一种新的、变革性的抗生素技术。抗生素，产生AMP的益生菌将被用来减少家禽肠道中的病原体。禽类肠道中的病原体被认为是禽肉加工过程中受污染的主要来源。AMP是一种具有显著杀菌性能的小蛋白质。益生菌将作为AMP递送载体进行测试。益生菌是一种耐胆汁的微生物，可以在食物或水中安全地输送。人工合成的生物DNA启动子区域将被用来精确控制感染部位的AMP的传递。将在肠炎沙门氏菌(一种常见的食源性病原体)挑战的家禽中检查可控AMP传递的影响。将检查活的生物治疗细菌对家禽胃肠道中存在的微生物区系的影响。该项目将在发现/开发方面取得以下进展：1)发现选择性针对沙门氏菌的抗菌肽。2)开发用于益生菌的多肽表达和分泌盒；3)开发竞争性抑制沙门氏菌生长的益生菌；4)开发可安全供应给农场动物的益生菌；以及5)开发积极调节家禽肠道微生物群的益生菌。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop technology to reduce pathogenic salmonella carriage in poultry. The challenge addressed is the one of foodborne bacterial gastrointestinal infections. These infections are significant causes of morbidity and mortality worldwide. Of alarming concern is the emergence of bacteria that are resistant to antibiotics. A major source of drug-resistance development is the widespread use of antibiotics in animal production. An estimated 70% of all antibiotics produced in the US are administered to livestock, primarily to promote growth and improve feed efficiency, even in the absence of infection. This sub-therapeutic administration of antibiotics to animals creates a vast reservoir for the selection of drug-resistant bacteria. As a potential solution to this problem, probiotic bacteria will be engineered that express and secrete antimicrobial peptides (AMPs) in the gastrointestinal (GI) tract of animals. In this application, the focus is on chickens, a significant source of animal protein in diets around the globe. Foodborne Salmonella infects millions of people in the US every year, and the major source of Salmonella poisoning are poultry products. The goal is to reduce carriage of Salmonella in chickens to ensure safe food and reduce the need for antibiotics.This Small Business Innovation Research Phase I project will assess a new, transformative antibiotic technology. Antibiotic, AMP-producing probiotics will be used to reduce pathogens in poultry intestines. Pathogens in poultry intestines are considered the major source of contamination of poultry meat during processing. AMPs are small proteins with remarkable bactericidal properties. Probiotics will be tested as AMP-delivery vehicles. Probiotics are bile-resistant microorganisms that can be delivered safely in food or water. Synthetic biological DNA promoter regions will be employed to precisely control the delivery of AMPs at the site of infection. The impact of controllable AMP delivery will be examined in poultry challenged by Salmonella Enteritidis, a common foodborne pathogen. The impact will be examined for live biotherapeutic bacteria on the microbiota present in the GI tracts of poultry. This project will result in the following advances in discovery/development: 1) Discovery of antimicrobial peptides that selectively target Salmonella spp. 2) Development of peptide expression and secretion cassettes for probiotics; 3) Development of probiotics that competitively inhibit the growth of Salmonella spp.; 4) Development of probiotics that may be supplied safely to farm animals; and 5) Development of probiotics that positively modulate the gut microbiome of poultry.