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

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是开发减少家禽中致病性沙门氏菌携带的技术。解决的挑战是食源性细菌胃肠道感染之一。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%用于牲畜，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。这种对动物的抗生素亚治疗给药为耐药细菌的选择创造了巨大的储存库。 作为该问题的潜在解决方案，益生菌将被工程化以在动物的胃肠道（GI）中表达和分泌抗菌肽（AMP）。在此应用中，重点是鸡，这是地球仪饮食中动物蛋白的重要来源。食源性沙门氏菌每年在美国感染数百万人，沙门氏菌中毒的主要来源是家禽产品。其目标是减少沙门氏菌在鸡中的携带，以确保食品安全，并减少对抗生素的需求。这个小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，AMP生产益生菌将用于减少家禽肠道中的病原体。家禽肠道中的病原体被认为是禽肉加工过程中的主要污染源。AMP是具有显著杀菌特性的小蛋白质。益生菌将作为AMP递送载体进行测试。益生菌是胆汁抗性微生物，可以安全地在食物或水中提供。将采用合成的生物DNA启动子区来精确控制AMP在感染部位的递送。将在受沙门氏菌（一种常见的食源性病原体）攻击的家禽中检查可控AMP递送的影响。将检查活生物多样性细菌对家禽胃肠道中存在的微生物群的影响。该项目将在发现/开发方面取得以下进展：1）发现选择性靶向沙门氏菌的抗菌肽。2)开发用于益生菌的肽表达和分泌盒; 3）开发竞争性抑制沙门氏菌生长的益生菌; 4)开发可以安全地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组的益生菌。

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.