Bacillus Subtilis Feed Probiotics for Antibiotic-Sensitive Pathogen Inhibition
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Solution Overview
Problem
There is a need for probiotic strains that can effectively inhibit E. coli and Clostridium perfringens in animals, particularly in poultry, to improve health and performance parameters such as weight gain, feed conversion ratio, and reduce necrotic enteritis, while being sensitive to antibiotics and suitable for use in animal feed additives.
Innovation Solution
Development of Bacillus subtilis strains DSM32324 and DSM32325, and their mutants, which are sensitive to antibiotics and exhibit inhibitory activity against E. coli and Clostridium perfringens, formulated as Direct Fed Microbials (DFMs) or animal feed additives, capable of surviving pelleting processes and improving animal performance through spore formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If antibiotic growth promoters are used, then animal performance parameters improve, but antibiotic resistance develops and safety concerns arise
Solution Approach 1:
The patent converts the harmful effect of antibiotic resistance into a benefit by selecting Bacillus subtilis strains that are inherently sensitive to multiple antibiotics while producing antimicrobial substances (bacitracin, polymyxin B, colistin) that inhibit pathogenic bacteria. This allows the probiotic to provide growth-promoting effects without contributing to antibiotic resistance, effectively turning the resistance problem into a selection criterion for safe strains
Solution Approach 2:
The patent uses Bacillus subtilis strains as intermediary organisms that produce antimicrobial substances to indirectly control pathogenic bacteria. Instead of directly applying antibiotics to animals, the probiotic strains serve as mediators that generate natural antimicrobials (bacitracin, polymyxin B, colistin) to inhibit E. coli and C. perfringens, thereby improving animal performance without the harmful effects of direct antibiotic administration
2Reliability
If probiotic strains are selected for inhibitory activity against pathogens, then animal health improves, but the strains may exhibit antibiotic resistance
Solution Approach 1:
The patent changes the selection parameters for probiotic strains by imposing strict antibiotic sensitivity criteria. Strains must be sensitive to ampicillin, vancomycin, gentamicin, kanamycin, streptomycin, erythromycin, clindamycin, tetracycline, and chloramphenicol while simultaneously demonstrating inhibitory activity against E. coli and C. perfringens. This parameter change ensures that only strains providing pathogen inhibition without antibiotic resistance risks are selected
Solution Approach 2:
The patent applies different quality requirements to different functional aspects of the probiotic strain. The strain must exhibit antimicrobial production capability (inhibitory activity) against specific pathogens while maintaining antibiotic sensitivity. This local quality differentiation allows the strain to be effective against pathogens through natural antimicrobial substances rather than through antibiotic resistance mechanisms
3Duration of action of stationary object
If Bacillus strains are used as Direct Fed Microbials, then they survive pelleting processes, but efficacy against pathogens must be maintained
Solution Approach 1:
The patent performs preliminary selection of Bacillus subtilis strains that possess both heat resistance (to survive pelleting at 90-95°C) and antimicrobial production capability before formulation as Direct Fed Microbials. This preliminary action ensures that only strains meeting both criteria are selected, maintaining efficacy against pathogens while ensuring survival through the pelleting process
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The Bacillus subtilis strains significantly reduce necrotic enteritis lesions and mortality, enhance weight gain, and improve feed conversion ratios in poultry, demonstrating improved performance parameters comparable to or better than antibiotic treatments.
Implementation Method 1
These products are relevant for the feed industry because spores are heat stable and can survive the pelletizing process at temperatures up to 90-95° C.
Implementation Method 2
The Bacillus subtilis strains DSM32324 and DSM32325 inhibit the growth of Escherichia coli and Clostridium perfringens in vitro and in vivo
Data Source
AI summary
The present invention provides a Bacillus subtilis strain selected from the group consisting of a) the strain deposited as DSM32324,b) the strain deposited as DSM32325, and c) a mutant strain of (a) or (b) which has sensitivity for ampicillin, vancomycin, gentamicin, kanamycin, streptomycin, erythromycin, clindamycin, tetracycline, and chloramphenicol; and has inhibitory activity against E. coli and Clostridium perfringens. The invention further relates to Bacillus compositions comprising at least one Bacillus subtilis strain of the invention, preferably the Bacillus subtilis strain DSM32324 and/or the Bacillus subtilis strain DSM32325, as Direct Fed Microbial (DFM), premix, animal feed additive or animal feed. The invention provides a method of improving one or more animal performance parameters selected from the group consisting of i) increased weight gain (WG), ii) lower feed conversion ratio (FCR), iii) lower necrotic enteritis lesion scoring, iv) lower necrotic enteritis frequency, v) lower necrotic enteritis mortality, vi) increased European Production Efficacy Factor (EPEF), and vii) lower mortality, by feeding a strain or a composition according to the invention to an animal.