Bacterial infections evading the current antibiotic arsenal warrant new treatment options. The mainstay treatment for Clostridium difficile infections involves administration of the broad-spectrum antibiotic vancomycin, which also depletes the gut microbiome and its natural defenses. This leads to recurrent C. difficile infections in 20-30% of patients. Alternative treatment options are limited, triggering a perpetual cycle of relapse and recovery that may eventually lead to death. Keratinicyclin B represents a glycopeptide antibiotic chemotype with a mechanism of action that is selective for Clostridia. When combined, vancomycin (or other glycopeptide antibiotic) and keratinicyclin B interact synergistically to inhibit the growth of C. difficile at concentrations far lower than their respective minimal inhibitory concentrations. Such a combination therapy could allow for targeted colonization clearance at low antibiotic doses, thereby minimizing toxicity and reducing the likelihood of relapse.

The present disclosure provides modified bacteria and modified peptidoglycan comprising modified D-amino acids; compositions comprising the modified bacteria or peptidoglycan; and methods of using the modified bacteria or peptidoglycan. The modified D-amino acids include a bioorthogonal functional group such as an azide, an alkyne or a norbornene group. Also provided are modified peptidoglycans conjugated to a molecule of interest via a linker.

The present disclosure provides modified bacteria and modified peptidoglycan comprising modified D-amino acids; compositions comprising the modified bacteria or peptidoglycan; and methods of using the modified bacteria or peptidoglycan. The modified D-amino acids include a bioorthogonal functional group such as an azide, an alkyne or a norbornene group. Also provided are modified peptidoglycans conjugated to a molecule of interest via a linker.

Vancomycin conjugates of Formula I, its stereoisomers, prodrugs, pharmaceutically acceptable salts, and metal coordination complexes thereof is described in the present disclosure. Further, the present disclosure relates to pharmaceutical compositions comprising vancomycin conjugates, its stereoisomers, prodrugs, pharmaceutically 10 acceptable salts, metal coordination complex thereof with one or more other pharmaceutical compositions or an antibiotic. The present disclosure also describes a process of preparing said conjugates, its stereoisomers, prodrugs, pharmaceutically acceptable salts, and metal coordination complex thereof, and pharmaceutical compositions as described above. Furthermore, the present disclosure describes 15 compositions and methods of treating conditions and diseases that are mediated by bacteria

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The present invention provides oligopeptides, in particular, Ang-(1-7) derivatives, and methods for using and producing the same. In one particular embodiment, oligopeptides of the invention have higher blood-brain barrier penetration and/or in vivo half-life compared to the native Ang-(1-7), thereby allowing oligopeptides of the invention to be used in a wide variety of clinical applications including in treatment of cognitive dysfunction and pain.

A vaccine construct comprising an antigenic PCSK9 peptide and an immunogenic carrier, and methods of using the same that are effective to lower blood cholesterol levels in a mammal and treat dyslipidemias and related disease states in a mammal without the frequency of administration required by passive immunity strategies.

A vaccine construct comprising an antigenic PCSK9 peptide and an immunogenic carrier, and methods of using the same that are effective to lower blood cholesterol levels in a mammal and treat dyslipidemias and related disease states in a mammal without the frequency of administration required by passive immunity strategies.

Disclosed herein is a rapid genetics-free method for eliciting and detecting cryptic metabolites using an imaging mass spectrometry-based approach. An organism of choice is challenged with elicitors from a small molecule library. The molecules elicited are then imaged by mass spec, which allows for rapid identification of cryptic metabolites. These are then isolated and characterized. Employing the disclosed approach activated production of cryptic glycopeptides from an actinomycete bacterium. The molecules that result, the keratinimicins and keratinicyclins, are metabolites with important structural features. At least two of these, keratinimicins B and C, are highly bioactive against several pathogenic strains. This approach will allow for rapid activation and identification of cryptic metabolites from diverse microorganisms in the future.

Disclosed are methods, systems, components, and compositions for cell-free synthesis of glycosylated proteins. The glycosylated proteins may be utilized in vaccines, including anti-bacterial vaccines. The glycosylated proteins may include a bacterial polysaccharide conjugated to a carrier, which may be utilized to generate an immune response in an immunized host against the polysaccharide conjugated to the carrier. The glycosylated proteins may be synthesized in cell-free glycoprotein synthesis (CFGpS) systems using prokaryote cell lysates that are enriched in components for glycoprotein synthesis such as oligosaccharyltransferases (OSTs) and lipid-linked oligosaccharides (LLOs) including OSTs and LLOs associated with synthesis of bacterial O antigens.

Provided herein are glycosylated peptide amphiphiles (GPAs), supramolecular glyconanostructures assembled therefrom, and methods of use thereof. In particular, provided herein are glycosaminoglycan (GAG) mimetic peptide amphiphiles (PAs) and supramolecular GAG mimetic nanostructures assembled therefrom that mimic the biological activities of GAGs, such as heparin, heparan sulfate, hyaluronic acid etc.