Research Institute at Nationwide Children's Hospital

University of Southern California

The Ohio State University

Trellis Bioscience, Inc.

University of California

Nationwide Children's Hospital, Inc.

Steven David Goodman

Lauren Opremcak Bakaletz

Gail E Besner

Michael Bailey

Lawrence M Kauvar

Reyna J Simon

Angeles Estelles

Stefan Ryser

Olga Kay

Wenyuan Shi

Fengxia Qi

Sheryl S Justice

Lauren Mashburn Warren

Amal Amer

Provided herein are methods and probiotic compositions for treating or preventing a disease or neurodevelopmental deficiency in a subject in need thereof using the compositions. Aspects and embodiments of this technology combine the health benefits of probiotic bacteria with prebiotic substances to help stimulate the exclusive growth of the probiotic species and, in one aspect, provide the bacteria in the form of a biofilm on a biocompatible microsphere.

Prebiotic formulations for prevention of sepsis and necroenterocolitis induced neurodevelopmental deficiencies

The disclosure provides methods and compositions that are useful to lessen and/or cure bacterial biofilms and treat diseases or disorders associated with biofilms using one or more novel polypeptide vaccines, antibodies, antibody fragments and compositions. Bacteria that cannot form functional biofilms are more readily cleared by the remainder of the host's immune system and/or traditional antibiotics.

DNABII vaccines and antibodies with enhanced activity

Provided herein are derivatives of HMGB1 that have been engineered to possess the same efficacious anti-bio film activity but are smaller and do not induce inflammation.

HMGB1 protein derivatives for the removal of biofilms

This disclosure provides isolated or recombinant polypeptides that are useful to vaccinate individuals suffering from chronic/recurrent biofilm disease or as a therapeutic for those with an existing infection. The individual's immune system will then naturally generate antibodies which prevent or clear these bacteria from the host by interfering with the construction and or maintenance of a functional protective biofilm. Alternatively, antibodies to the polypeptides can be administered to treat or prevent infection. Bacteria that are released from the biofilm by our technology are more readily cleared by the remainder of the host's immune system.

Peptides and antibodies for the removal of biofilms

This disclosure provides isolated or recombinant polypeptides that are useful to vaccinate individuals suffering from chronic/recurrent biofilm disease or as a therapeutic for those with an existing infection. The individual's immune system will then naturally generate antibodies which prevent or clear these bacteria from the host by interfering with the construction and or maintenance of a functional protective biofilm. Alternatively, antibodies to the polypeptides can be administered to treat or prevent infection. Bacteria that cannot form functional biofilms are more readily cleared by the remainder of the host's immune system and/or traditional antibiotics.

Compositions and methods for the removal of biofilms

Provided herein are methods and compositions for disrupting bio films in vitro and in vivo. Also disclosed are antibodies comprising a specified heavy chain (HC) immunoglobulin variable domain sequence and/or a specified light chain (LC) immunoglobulin variable domain sequence.

Antibody compositions for disrupting biofilms

Provided herein are methods to inhibit or disrupt a bio film comprising contacting the bio film with an agent that cleaves the Holliday junction (HJ) structure in the bio film.

Compositions and methods for enzymatic disruption of bacterial biofilms

Binding agents able to disrupt bacterial biofilms of diverse origin are described, including monoclonal antibodies secreted by human B lymphocytes. Methods to prevent formation of or to dissolve biofilms with these binding agents are also described. Immunogens for eliciting antibodies to disrupt biofilms are also described.

Binding moieties for biofilm remediation

Disclosed are approaches to determining a sensitivity of a bacterium to a given antibiotic and generating targeted treatments based on the sensitivity. One or more antibiotics may be selected for a chronic/recurrent infection resulting from a biofilm so as to reduce dose and or length of course of antibiotic treatment. For example, if a bacterial pathogen is determined to be sensitive to an antibiotic in its planktonic form but resistant to that antibiotic in its biofilm form, then the biofilm may be dispersed or disrupted from the biofilm residence in order to clear the infection. In various embodiments, a dispersal or disruption method and/or agent may be determined based at least in part on a rate of bacterial release from a biofilm that sensitizes the pathogen to a chosen antibiotic.

Methods for determining antibiotic sensitivity

This disclosure provides antibody fragments and isolated polypeptides comprising the antibody fragments that are useful as a therapeutic for those with an existing infection characterized by the formation of biofilms. Antibody fragments and isolated polypeptides comprising the antibody fragments can be administered to detect, treat, or prevent infection and/or remediate biofilms. Bacteria that cannot form functional biofilms are more readily cleared by the remainder of the host's immune system and/or traditional antibiotics.

Antibody fragments for the treatment of biofilm-related disorders

Methods of breaking down a biofilm or inhibiting, preventing or treating a microbial infection that produces a biofilm are disclosed, which involves administration of a polypeptide that has one or more modified HMG-box 1 domains to a subject suffering from the infection or having the biofilm. By competing with microbial proteins that bind to DNA scaffold in the biofilm, these polypeptides destabilize the biofilm leading to destruction and removal of the biofilm by the immune system.

Composition and methods for disruption of bacterial biofilms without accompanying inflammation

Methods of and compositions for breaking down a biofilm or inhibiting, preventing or treating a microbial infection that produces a biofilm are disclosed, which involves administration of an interfering agent capable of specifically competing, titrating, or inhibiting the binding of an HU protein to a microbial DNA. By competing with HU proteins that bind to DNA scaffold in the biofilm, these interfering agents destabilize the biofilm leading to destruction and removal of the biofilm by the immune system. Further method and composition aspects are contemplated in relation to infections caused by bacteria that export an HU protein.

Growing community of inventors

Hilliard, OH, United States of America

Steven David Goodman