Technological strategies for administration of an antivirulence compound against salmonellosis in farm animals

• Grant number: 18/22412-2
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: October 01, 2019
• End date: August 31, 2020
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Vânia Santos Braz
• Grantee: Vânia Santos Braz
• Company: Biosmart Nanotechnology Ltda
• CNAE: Atividades de apoio à pecuária
• City: Araraquara
• Associated researchers: Marlus Chorilli
• Associated scholarship(s): 19/20637-0 - Investigation of in vivo antivirulence activity of microencapsulated LED209 nanoemulsion, BP.TT; 19/20690-8 - Obtaining the LED209-containing nanoemulsion and its microencapsulation, BP.TT; 19/21081-5 - Technological strategies for administration of an antivirulence compound against salmonellosis in farm animals, BP.PIPE

Abstract

In 2017, Brazil ranked second as a producer of chicken meat and the fourth of pork meat in the rank of the world market, according to the report of ABPA (Brazilian Association of Animal Protein). 33.1% of chicken and 18.5% of pork meat from this production were destined to export, that places us in a competitive and important international market for the Brazilian economy. Therefore, there is a concern about stop the use of antibiotics in animal livestock, which are commonly used to prevent infections and as growth promoters. On the other hand, it is necessary to secure control of bacterial infections, which may cause export and domestic consumption unviable. The huge rise of bacterial resistance, both to clinical as environmental isolates. It has been highlighted and warned for the beginning of a pronounced post-antibiotic Era. This has led to a worldwide concern and a critical need to develop new therapeutic and/or preventive alternatives against infectious diseases. Many countries, especially in Europe, have already encouraged restrictions on the use of antibiotics as growth promoters. One approach that has been raising is the use of antivirulence compounds that are able to disarm bacterial pathogens interrupting the disease progression, such as the LED209, characterized by potential capacity antivirulence, being able to inhibit the QseC signaling cascade, a histidine kinase found in many pathogenic bacteria, such as Salmonella. QseC senses autoinducer 3 (AI-3) produced by bacteria, and the adrenergic hormones epinephrine/norepinephrine produced by the host and is responsible for initiating a regulatory cascade of several virulence genes. However, LED209 has a low aqueous solubility, being extremely important the search for an efficient carrier for this molecule. The main objective of this project is to evaluate technological strategies for the administration of this antivirulence compound in the fight against Salmonellosis in farm animals. Therefore, it is intended to obtain an efficient vehicle, such as a nanoemulsion, in that way avoiding the use of toxic organic solvents, followed by microencapsulation with pH-dependent polymers, which will promote the release of the LED209 molecule in the animal gut. To proof of viability, in this phase 1, two aspects will be evaluated: (1) obtaining the nanoemulsion containing LED209 and its microencapsulation; and (2) antivirulence capacity of the microencapsulated LED209 nanoemulsion in mice challenged with Salmonella. After the viability of using this system, the proposal for Phase 2 will be to add this system in the diet and to perform tests in larger animals, such as pigs and chicken, in the same way and to substitute the antibiotic-growth-promoters currently used. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRAZ, VANIA SANTOS; MELCHIOR, KARINE; MOREIRA, CRISTIANO GALLINA. Escherichia coli as a Multifaceted Pathogenic and Versatile Bacterium. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, DEC 21 2020. (14/06779-2, 19/03049-7, 18/22412-2, 18/22042-0)