US-12616663-B2 - Plant-derived exosome-like nanoparticles inhibit bacterial pathogenicity

US12616663B2US 12616663 B2US12616663 B2US 12616663B2US-12616663-B2

Abstract

Provided are methods for preventing and/or treating oral diseases, disorders, and/or conditions. In some embodiments, the methods relate to administering to the oral cavity of a subject in need thereof a composition that includes an effective amount of ginger-derived exosome-like nanoparticles (GELNs) or a biologically active component thereof. Also provided are methods for preventing and/or treating periodontitis, methods for reducing growth of and/or pathogenicity of microorganisms in the oral cavities of subjects, methods for reducing microorganismal motility, and methods for reducing bone loss in the oral cavities of subjects associated with infection with microorganisms. Also provided are compositions that can be employed in the disclosed methods.

Inventors

Huang-Ge Zhang

Assignees

UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.

Dates

Publication Date: 20260505
Application Date: 20200302

Claims (10)

1 . A method for inhibiting and/or treating periodontitis or oral disease associated with a Porphyromonas gingivalis ( P. gingivalis ) infection, the method comprising administering to the oral cavity of a subject in need thereof a composition comprising a ginger-derived exosome-like nanoparticles (GELNs) or a biologically active component thereof; wherein the GELN can be obtained in bands between the 8%/30% layer and the 30%/45% layer of a sucrose step gradient; and wherein the GELN or the biologically active component is provided in an amount that is therapeutically effective for the inhibition and/or treatment of periodontitis or oral disease associated with a P. gingivalis infection.
2 . The method of claim 1 , wherein the biologically active component comprises a lipid, a protein, an miRNA, or a combination thereof.
3 . The method of claim 2 , wherein the biologically active component comprises one or more miRNAs, optionally wherein the one or more miRNAs comprise an miR-159a-3p miRNA.
4 . The method of claim 2 , wherein the biologically active component comprises one or more lipids, optionally wherein the one or more lipids comprises phosphatidic acid (PA).
5 . The method of claim 4 , wherein the one or more lipids comprises PA (34:2).
6 . A method for reducing growth of Porphyromonas gingivalis ( P. gingivalis ) in the oral cavity of a subject, the method comprising administering to the oral cavity of the subject a composition comprising a ginger-derived exosome-like nanoparticles (GELNs) or a biologically active component thereof; wherein the GELN can be obtained in bands between the 8%/30% layer and the 30%/45% layer of a sucrose step gradient; and wherein the GELN or the biologically active component is provided in an amount that is therapeutically effective for the inhibition and/or treatment of periodontitis or oral disease associated with a P. gingivalis infection.
7 . The method of claim 6 , wherein the biologically active component comprises a lipid, a protein, an miRNA, or a combination thereof.
8 . The method of claim 6 , wherein the biologically active component comprises one or more miRNAs, optionally wherein the one or more miRNAs comprise an miR-159a-3p miRNA.
9 . The method of claim 6 , wherein the biologically active component comprises one or more lipids, optionally wherein the one or more lipids comprises phosphatidic acid (PA).
10 . The method of claim 9 , wherein the one or more lipids comprises PA (34:2).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a United States National Phase Entry of PCT International Patent Application No. PCT/US2020/020675, filed Mar. 2, 2020, incorporated herein by reference in its entirety and which claims the benefit of U.S. Provisional Patent Application Ser. No. 62/812,644, filed Mar. 1, 2019, the disclosure of which is incorporated herein by reference in its entirety. GOVERNMENT INTEREST This invention was made with government support under R01 AT008617 and UH3 TR000875 awarded by the National Institutes of Health. The government has certain rights in the invention. TECHNICAL FIELD The presently disclosed subject matter relates to compositions and methods for preventing and/or treating diseases, disorders, and conditions associated with microbial infections in subjects. More particularly, the presently disclosed subject matter relates to compositions comprising effective amounts of ginger-derived exosome-like nanoparticles (GELNs) or one or more biologically active component thereof and methods of use thereof to prevent and/or treat microbial infections and consequences thereof, particularly but not limited to microbial infections and consequences thereof in the oral cavity. BACKGROUND Chronic infectious diseases commonly involve large numbers of virulence factors, which target to several host factors in multiple pathways. Developing an effective therapeutic strategy that can inhibit most virulence factors of any given microorganism without causing undesirable side effects can benefit from a change of focus from delivering individual therapeutic agents to delivering packages of therapeutic agents that can target multiple virulence factors simultaneously. Currently, no such delivery vehicle or strategy that selectively targets pathogens and carries multiple therapeutic agents without also causing significant toxicity is available. Generally, edible plants are beneficial for human health and can help prevent and/or treat chronic infectious diseases. However, the cellular and molecular mechanisms underlying the therapeutic effects with respect to prevention and/or treatment of infectious disease are not known. Since ELNs naturally carry a large number and variety of molecules, it is possible that upon uptake of ELNs by infectious agents, ELN molecules could target multiple virulence factors simultaneously to prevent disease development. ELNs are derived from a healthy diet, and are unlikely to cause side-effects. As disclosed herein, ginger-derived ELNs (GELNs) were used to demonstrate that GELNs can have an effect on the prevention of Porphyromonas gingivalis (P. gingivalis) induced chronic periodontitis in a mouse model. Porphyromonas gingivalis (P. gingivalis), a Gram-negative anaerobic bacterium, is the major prevalent bacterium that contributes to chronic periodontitis, an inflammatory disease associated with an alteration of local microbiota. Periodontitis has been associated with cardiovascular disease, type 2 diabetes mellitus, and adverse pregnancy outcomes with an increased risk for delivery of premature labor and low-birth-weight infants. P. gingivalis expresses many virulence factors, including fimbriae (fimA and mfa1), gingipain [arginine-(Rgp) and lysine specific (Kgp)] proteases, lipopolysaccharides, hemagglutinin, and hemolysins that play an important role in the pathogenicity of the bacterium via tissue colonization, destruction, and interference with the host immune system. Fimbriae are protein-based filamentous appendages that protrude from P. gingivalis and facilitate adhesion to host cells and to other bacteria. Tissue degradation caused by proteolytic enzymes released from P. gingivalis contributes to periodontal biofilm formation and excessive immune stimulation. Orally delivering GELNs has been shown to lead to protection of mice against alcohol induced liver damage. That GELNs alter the gut microbiome composition and host physiology led us to test whether this strategy could be applied to treat and/or prevent oral infectious diseases. As disclosed herein, GELNs are selectively taken up by P. gingivalis, and upon being taken up, the pathogenicity of P. gingivalis is significantly reduced, including its growth, attachment, entry, proliferation in host cells, motility, and bone erosion in a mouse model. SUMMARY This summary lists several embodiments of the presently disclosed subject matter, and in many cases lists variations and permutations of these embodiments. This summary is merely exemplary of the numerous and varied embodiments. Mention of one or more representative features of a given embodiment is likewise exemplary. Such an embodiment can typically exist with or without the feature(s) mentioned; likewise, those features can be applied to other embodiments of the presently disclosed subject matter, whether listed in this summary or not. To avoid excessive repetition, this Summary does not list or suggest all possible combinations of suc