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Publication Number
US-11730780-B2
Publication Date
2023-08-22
Expiration Date
Abstract
The present invention relates to novel strains of lactic acid bacteria, more specifically, novel strains of Lactobacillus reuteri, capable of utilizing ethanolamine. This characteristic makes it possible for the bacteria to compete for the same substrate as pathogenic ethanolamine-utilizing pathogens, thereby presenting an effective means to combat infections resulting from such pathogenic bacteria. There is also provided a method of selecting further ethanolamine-utilizing lactic acid bacteria, as well as other methods and uses involving said novel strains and other ethanolamine-utilizing lactic acid bacteria.
Core Innovation
The invention relates to novel lactic acid bacterial strains capable of utilizing ethanolamine in the gastrointestinal tract. The strains are capable of using ethanolamine to compete with ethanolamine-utilizing pathogens and to inhibit pathogen growth and reduce virulence.
The disclosed strains comprise genes encoding ethanolamine ammonia lyase large subunit EutB, a gene encoding a microcompartment structural protein EutL, and/or a gene encoding an ethanolamine utilization protein EutH, and are capable of utilizing ethanolamine. The concept includes culturing with ethanolamine and confirming ethanolamine utilization, including confirming acetaldehyde production.
Optionally, the lactic acid bacteria include further genetic components, including an NADPH-dependent FMN reductase and/or a protein-tyrosine-phosphatase, and additional genes based on pfam03358/pfam13350. The disclosed use includes administration of such ethanolamine-utilizing lactic acid bacteria to treat or reduce the risk of developing conditions or disorders caused by or related to ethanolamine-utilizing pathogens, including formulation into probiotic compositions with frozen and/or lyophilized compositions.
Documented embodiments include Lactobacillus reuteri DSM 27131 and Lactobacillus reuteri DSM 32465. DSM 27131 and DSM 32465 are described as ethanolamine-positive by an acetaldehyde red-zone assay, and DSM 32465 is described as showing improved bile tolerance. Ex vivo results described in the partial content report strong inhibition of Clostridium difficile outgrowth by DSM 27131 versus a non-ethanolamine-utilizing strain (DSM 17938), supporting competition against an ethanolamine-utilizing pathogen.
Claims Coverage
The partial claim set includes three independent claims. Across them, the inventive scope centers on administering ethanolamine-utilizing lactic acid bacteria, optionally induced by ethanolamine during growth, characterized by specific ethanolamine utilization genes EutB/EutL and/or EutH, with optional further genetic components and treatment or reduction of risk directed to conditions caused by or related to ethanolamine-utilizing pathogens; one independent claim specifically limits the administered organism to Lactobacillus reuteri and uses culture with ethanolamine followed by retrieval.
Administering ethanolamine-utilizing lactic acid bacteria to treat or reduce risk of ethanolamine-pathogen-associated conditions
A method comprising administering to a subject an effective amount of lactic acid bacteria capable of utilizing ethanolamine produced by culturing in a culture medium comprising a gene encoding ethanolamine ammonia lyase large subunit EutB, a gene encoding a microcompartment structural protein EutL, and/or a gene encoding an ethanolamine utilization protein EutH, adding a first amount or concentration of ethanolamine at a first point in time and growing, optionally adding a second amount or concentration of ethanolamine at a second point in time and growing, and retrieving the lactic acid bacteria from said culture medium.
Induced ethanolamine-utilizing lactic acid bacteria administered after ethanolamine induction during growth
A method comprising administering to the subject an effective amount of lactic acid bacteria induced by ethanolamine during growth, wherein the lactic acid bacteria comprises a gene encoding ethanolamine ammonia lyase large subunit EutB, a gene encoding a microcompartment structural protein EutL, and/or a gene encoding an ethanolamine utilization protein EutH and is capable of utilizing ethanolamine.
Administering an ethanolamine-utilizing Lactobacillus reuteri strain produced by ethanolamine culturing and retrieval
A method comprising administering to the subject an effective amount of a Lactobacillus reuteri strain capable of utilizing ethanolamine, produced by culturing L. reuteri bacteria in a culture medium comprising a gene encoding ethanolamine ammonia lyase large subunit EutB, a gene encoding a microcompartment structural protein EutL, and/or a gene encoding an ethanolamine utilization protein EutH, adding to the culture medium of a first amount or concentration of ethanolamine at a first point in time and growing, optionally adding a second amount or concentration of ethanolamine at a second point in time and growing, and retrieving the L. reuteri bacteria from said culture medium.
Across the independent claims, the common inventive elements are administration to a subject of ethanolamine-utilizing lactic acid bacteria, including induced-by-ethanolamine embodiments, characterized by EutB/EutL and/or EutH capability, with culture medium ethanolamine addition during growth and retrieval for at least one independent claim; one independent claim also restricts the lactic acid bacteria to Lactobacillus reuteri.
Stated Advantages
Treating or reducing the risk of developing a condition or disorder caused by or related to an ethanolamine-utilizing pathogen in a subject.
Inhibiting pathogen growth and reducing virulence associated with ethanolamine-utilizing pathogens in the GI tract.
Dominant selection in the presence of ethanolamine-utilizing pathogens is supported by ethanolamine utilization and acetaldehyde production.
Improved bile tolerance is described for Lactobacillus reuteri DSM 32465.
Strong inhibition of Clostridium difficile outgrowth is described for Lactobacillus reuteri DSM 27131 versus a non-ethanolamine-utilizing strain.
Documented Applications
GI tract competition against ethanolamine-utilizing pathogens to inhibit pathogen growth and reduce virulence.
Treatment or risk reduction for dysbiosis caused by or related to an ethanolamine-utilizing pathogen.
Treatment or risk reduction for listeriosis caused by or related to an ethanolamine-utilizing pathogen.
Treatment or risk reduction for salmonellosis caused by or related to an ethanolamine-utilizing pathogen.
Treatment or risk reduction for bacterial infections leading to inflammatory bowel disorders caused by or related to an ethanolamine-utilizing pathogen.
Treatment or risk reduction for infections with pathogenic pseudomonades in infected wounds caused by or related to an ethanolamine-utilizing pathogen.
Treatment or risk reduction for tourist diarrhea caused by or related to an ethanolamine-utilizing pathogen.
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