IP Library › Granted Patent US 12,414,971
Granted Patent B2
US 12,414,971 · App. 17/279,386 · Granted Sep 16, 2025

Methods and compositions to treat and prevent infection

Inventors: Neeraj K. Surana (Durham, NC); Dennis Kasper (Cambridge, MA)
Assignees: DUKE UNIVERSITY; PRESIDENT AND FELLOWS OF HARVARD COLLEGE; CHILDREN'S MEDICAL CENTER CORPORATION
A61K35/747A23L33/135A23V2400/173
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Quick Facts
Patent No.
US 12,414,971
App. No.
17/279,386
Granted
Sep 16, 2025
Kind
B2
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.

Claims (13)

1. A method of increasing the levels of a Reg3 peptide in a subject in need thereof, comprising administering to the subject bacteria strain Ruminococcus gnavus, Lactobacillus reuteri or a combination thereof in an amount effective to increase the level of Reg3 peptide in the subject.

2. The method of claim 1 , wherein the Reg3 peptide is Reg3a, Reg3γ, or Reg3β.

3. The method of claim 1 , wherein the subject has an inflammatory condition.

4. The method of claim 1 , wherein the subject has a bacterial infection.

5. The method of claim 4 , wherein the bacterial infection is a gram-negative or gram-positive bacterium.

6. The method of claim 5 , wherein the bacteria is gram positive and selected from the group consisting of an enterococci infection, a vancomycin-resistant enterococci (VRC) infection, a Clostridium difficile infection, a Staphylococcus aureus infection, a methicillin-resistant Staphylococcus aureus (MRSA) infection, and a combination thereof.

7. The method of claim 4 , wherein the bacterial infection is caused by an antibiotic resistant pathogen.

8. The method of claim 1 , wherein the Ruminococcus gnavus, Lactobacillus reuteri or combination thereof is in a composition formulated for oral administration or rectal administration.

9. The method of claim 1 , wherein the Ruminococcus gnavus, Lactobacillus reuteri , or combination thereof is formulated for topical or inhalant administration.

10. The method of claim 1 , wherein the Ruminococcus gnavus, Lactobacillus reuteri , or combination thereof are live, replication competent bacteria.

11. The method of claim 1 , wherein the Ruminococcus gnavus, Lactobacillus reuteri , or combination thereof are not live, replication competent bacteria.

12. The method of claim 11 , wherein the Ruminococcus gnavus, Lactobacillus reuteri , or combination thereof is in the form of a bacterial lysate.

13. The method of claim 1 , wherein the Reg3 is Reg3γ and increases the stem cell proliferation within the gut of the subject.

Assignments (3)
CONFIRMATORY LICENSE Recorded Jan 16, 2024
From: DUKE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066338/0354 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 10, 2021
From: KASPER, DENNIS
To: DUKE UNIVERSITY
Reel/Frame 056497/0212 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 10, 2021
From: SURANA, NEERAJ K.
To: DUKE UNIVERSITY; PRESIDENT AND FELLOWS OF HARVARD COLLEGE; CHILDREN'S MEDICAL CENTER CORPORATION
Reel/Frame 056497/0393 →
Continuity (2)
Provisional Application 62736114 · Sep 25, 2018
Related Publication 20210386799A1 · Dec 16, 2021
References Cited (48)
US 5439678A · Dobrogosz et al. · 1995 [cited by applicant]
US 10376563B1 · Van Pijkeren et al. · 2019 [cited by applicant]
US 20120027736A1 · Morita et al. · 2012 [cited by applicant]
US 20150306156A1 · Borody · 2015 [cited by applicant]
US 20160120915A1 · Blaser et al. · 2016 [cited by applicant]
EP 2674162A1 · 2013 [cited by applicant]
WO 2010124387A1 · 2010 [cited by applicant]
WO 2014145958A2 · 2014 [cited by applicant]
Natividad et al., Applied and environmental Microbiolgy, 2013, vol. 79, No. 24, p. 7745-7754doi:10.1128/AEM.02470-13. (Year: 2013). [cited by examiner]
Kim et al., Intest Res. Jan. 2014;12(1):20-33. doi: 10.5217/ir.2014.12.1.20. Epub Jan. 28, 2014. PMID: 25349560; PMCID: PMC4204685. (Year: 2014). [cited by examiner]
Huang et al., Front. Immunol., Sep. 3, 2017, Sec. Microbial Immunology, vol. 8—2017; doi.org/10.3389/fimmu.2017.01063. (Year: 2017). [cited by examiner]
Acton et al, “Intestinal carriage of [cited by applicant]
Boyce et al, “Frequency and possible infection control implications of gastrointestinal colonization with methicillin-resistant [cited by applicant]
Brandl et al, “Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits,” Nature, Oct. 2008, pp. 804-807, 455. [cited by applicant]
Cash et al, “Symbiotic bacteria direct expression of an intestinal bactericidal lectin,” Science, Aug. 2006, pp. 1126-1130, 313(5790). [cited by applicant]
Choi et al, “Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia,” Journal of Experimental Medicine, Mar. 2013, pp. 551-561, 210(3). [cited by applicant]
Chung et al, “Gut immune maturation depends on colonization with a host-specific microbiota,” Cell, Jun. 2012, pp. 1578-1593, 149(7). [cited by applicant]
Darnaud et al, “Enteric Delivery of Regenerating Family Member 3 alpha Alters the Intestinal Microbiota and Controls Inflammation in Mice With Colitis,” Gastroenterology, Mar. 2018, pp. 1009-1023, 154(4). [cited by applicant]
Geva-Zatorsky et al, “Mining the Human Gut Microbiota for Immunomodulatory Organisms,” Cell, Feb. 2017, pp. 928-943, 168(5). [cited by applicant]
International Searching Authority, International Search Report and Written Opinion for corresponding International Application PCT/US2019/052895, mailed Dec. 17, 2019, 4 pages. [cited by applicant]
Islam et al, “Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator,” Nature Medicine, Feb. 2001, pp. 180-185, 7(2). [cited by applicant]
Jones et al, “Probiotic Lactobacillus reuteri Biofilms Produce Antimicrobial and Anti-inflammatory Factors,” BMC Microbiology, Dec. 2009, pp. 1-9, 9. [cited by applicant]
Kandler et al, “ [cited by applicant]
Lehotzky et al, “Molecular basis for peptidoglycan recognition by a bactericidal lectin,” Proceedings of the National Academy of Sciences, Apr. 2010, pp. 7722-7727, 107(17). [cited by applicant]
Mazmanian et al, “An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system,” Cell, Jul. 2005, pp. 107-118, 122(1). [cited by applicant]
Miki et al, “The bactericidal activity of the C-type lectin RegIIIbeta against Gram-negative bacteria involves binding to lipid,” Journal of Biological Chemistry, Oct. 2012, pp. 34844-34855, 287(41). [cited by applicant]
Misawa et al, “ [cited by applicant]
Mukherjee et al, “Regulation of C-type lectin antimicrobial activity by a flexible N-terminal prosegment,” Journal of Biological Chemistry, Feb. 2009, pp. 4881-4888, 284(8). [cited by applicant]
Mukherjee et al, “Antibacterial membrane attack by a pore-forming intestinal C-type lectin,” Nature, Jan. 2014, pp. 103-107, 505(7481). [cited by applicant]
Mukherjee et al, “Antimicrobial defense of the intestine,” Immunity, Jan. 2015, pp. 28-39, 42(1). [cited by applicant]
Pai et al, “Transplantation outcomes for severe combined immunodeficiency, 2000-2009,” New England Journal of Medicine, Jul. 2014, pp. 434-446, 371(5). [cited by applicant]
Peng et al, “Update on Antimicrobial Resistance in Clostridium difficile: Resistance Mechanisms and Antimicrobial Susceptibility Testing. Journal of Clinical Microbiology,” Journal of Clinical Microbiology, Apr. 2017, p… [cited by applicant]
Peschel et al, “Inactivation of the dit operon in [cited by applicant]
Peters et al, “Antimicrobial peptides: primeval molecules or future drugs?” PLoS pathogens, Oct. 2010, 6(10):e1001067. [cited by applicant]
Robey et al, “Identification of Legionella pneumophila rcp, a pagP-like gene that confers resistance to cationic antimicrobial peptides and promotes intracellular infection,” Infection and Immunity, Jul. 2001, pp. 4276-… [cited by applicant]
Rubio et al, “The Natural Antimicrobial Enzyme Lysozyme is Up-Regulated in Gastrointestinal Inflammatory Conditions,” Pathogens, Jan. 2014, pp. 73-92, 3(1). [cited by applicant]
Sadighi Akha et al, “Acute infection of mice with Clostridium difficile leads to elF2α phosphorylation and pro-survival signalling as part of the mucosal inflammatory response,” Immunology, Sep. 2013, pp. 111-122, 140(1… [cited by applicant]
Shintani et al, “Validation of Sterilization Procedures and Usage of Biological Indicators in the Manufacture of Healthcare Products,” Biocontrol Science, 2011, pp. 85-94, 16(3). [cited by applicant]
Sieprawska-Lupa et al, “Degradation of human antimicrobial peptide LL-37 by [cited by applicant]
Stelter et al, “ [cited by applicant]
Surana et al, “Moving beyond microbiome-wide associations to causal microbe identification,” Nature, Dec. 2017, pp. 244-247, 552(7684). [cited by applicant]
Ubeda et al, “Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans,” The Journal of Clinical Investigation, Dec. 20… [cited by applicant]
Vaishnava et al, “Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host- microbial interface,” Proceedings of the National Academy of Sciences, Dec. 2008, pp. 20858-20863, 105(52). [cited by applicant]
Vaishnava et al, “The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine,” Science, Oct. 2011, pp. 255-258, 334(6053). [cited by applicant]
Van Ampting et al, “Intestinally secreted C-type lectin Reg3b attenuates salmonellosis but not listeriosis in mice,” Infection and Immunity, Mar. 2012, pp. 1115-1120, 80(3). [cited by applicant]
Wang et al, “Intestinal REG3 Lectins Protect against Alcoholic Steatohepatitis by Reducing Mucosa-Associated Microbiota and Preventing Bacterial Translocation,” Cell Host Microbe, Feb. 2016, pp. 227-239, 19(2). [cited by applicant]
Winer et al, “The Intestinal Immune System in Obesity and Insulin Resistance,” Cell Metabolism, Mar. 2016, pp. 413-426, 23. [cited by applicant]
Zhao et al, “Survival signal REG3a prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease,” The Journal of Clinical Investigation, Sep. 2018, pp. 4970-4979, 128(11). [cited by applicant]