Methods and compositions to treat and prevent infection
Inventors
Surana, Neeraj K. • Kasper, Dennis
Assignees
Boston Childrens Hospital • Harvard University • Duke University
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Publication Number
US-12414971-B2
Publication Date
2025-09-16
Expiration Date
Abstract
In certain aspects, described herein are methods, bacteria, and compositions for the treatment of bacterial infections. Specifically, bacteria that can upregulate antimicrobial peptides, e.g., Reg3, within a subject have been identified and methods of using such bacteria to treat infections is described.
Core Innovation
The invention relates to methods for increasing the levels of a Reg3 peptide in a subject in need thereof by administering bacteria strains Ruminococcus gnavus, Lactobacillus reuteri, or a combination thereof in an amount effective to increase the level of Reg3 peptide in the subject. The disclosed approach is directed to elevating Reg3 family peptides and is supported by experimental support described in the provided content.
The disclosure ties the administered bacteria to increased antimicrobial peptide levels, with Reg3α, Reg3γ, and Reg3β being increased, and with Paneth-cell effectors such as cryptdin 5/defensin 5 and lysozyme also being increased to reduce colonization, infection, and spread. The disclosure further connects the Reg3γ subtype to stem cell proliferation within the gut of the subject as a described outcome.
The invention is positioned for treatment and prevention contexts involving bacterial infections, including gram-positive and gram-negative pathogens, and includes antibiotic-resistant bacteria. Documented examples named in the provided content include VRE, MRSA, C. difficile, and Salmonella, and the disclosure also reports potential antiviral effects associated with cryptdin 5/defensin 5 upregulation.
Claims Coverage
Independent claim clm-00001 covers increasing Reg3 peptide levels by administering Ruminococcus gnavus, Lactobacillus reuteri, or a combination thereof. Dependent claims refine the bacterial strain form and Reg3 subtype and introduce additional context constraints such as infection gram character and association of a Reg3 subtype with stem cell proliferation.
Administering Reg3-inducing bacteria to increase Reg3 peptide levels
A method of increasing the levels of a Reg3 peptide in a subject by administering Ruminococcus gnavus, Lactobacillus reuteri, or a combination thereof in an amount effective to increase the level of Reg3 peptide in the subject.
Using live, replication-competent bacterial strains
The method further comprises administering live, replication-competent bacteria consisting of Ruminococcus gnavus and/or Lactobacillus reuteri.
Using non-live, non-replication-competent bacterial preparations
The method further comprises administering Ruminococcus gnavus and/or Lactobacillus reuteri that are not live and are not replication-competent bacteria.
Using a bacterial lysate form
The method further comprises using Ruminococcus gnavus, Lactobacillus reuteri, or a combination thereof in the form of a bacterial lysate.
Increasing Reg3γ to promote stem cell proliferation in the gut
The method further comprises increasing Reg3 where Reg3 is Reg3γ, thereby increasing stem cell proliferation within the gut of the subject.
Treating bacterial infections based on gram character
The method further comprises where the bacterial infection is caused by either a gram-negative or gram-positive bacterium.
Overall, the claim coverage focuses on raising Reg3 peptide levels through administration of Ruminococcus gnavus and/or Lactobacillus reuteri, with dependent features specifying live versus non-live/non-replication-competent forms, including bacterial lysate, linking Reg3γ to stem cell proliferation in the gut, and constraining infection context by gram character.
Stated Advantages
Increases the levels of a Reg3 peptide in a subject.
Reduces colonization, infection, and spread of gram-positive and gram-negative pathogens, including antibiotic-resistant bacteria.
Provides potential antiviral effects via upregulation of cryptdin 5/defensin 5.
Increases stem cell proliferation within the gut of the subject when Reg3 is Reg3γ.
Documented Applications
Treatment and prevention of bacterial infections caused by gram-positive or gram-negative bacteria, including antibiotic-resistant bacteria (named examples include VRE, MRSA, C. difficile, and Salmonella).
Use in colitis/inflammatory bowel disease and other inflammatory conditions as described in the provided content.
Use in contexts described as obesity and alcohol liver disease as provided in the provided content.
Potential antiviral activity associated with cryptdin 5/defensin 5 upregulation, with named antiviral contexts including adenovirus, HSV, influenza, HPV, and HIV.
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