Threoglucins Targeting Streptococcus Suis With Selective Antibacterial Action

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Solution Overview

Problem

Current antibiotics used to treat Streptococcus suis infections have a broad spectrum of activity, which can be toxic to human cells and beneficial bacteria, necessitating the development of targeted therapeutic agents.

Innovation Solution

The use of threoglucins, a family of small molecules with novel chemical structures, specifically targeting Streptococcus suis through a new mechanism of action, thereby minimizing impact on non-target bacteria and human cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibiotics are used to treat Streptococcus suis infections, then the bacterial infection can be treated, but the antibiotics are toxic to human cells and beneficial bacteria due to broad spectrum activity

Engineering Contradiction:

Improveantibacterial efficacyVSAvoidtoxicity to human cells and beneficial bacteria

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The threoglucin peptides exhibit local quality by demonstrating highly selective antibacterial activity specifically against Streptococcus suis while sparing human cells and beneficial bacteria. This selectivity is achieved through the unique chemical structure of threoglucins, which includes a C-terminal Tryptophan (Trp)-Tyrosine (Tyr) dyad and an intermediate 1,3-oxazinane modification, allowing targeted interaction with S. suis-specific cellular components without affecting human cell physiology

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention changes the key parameter of spectral specificity from broad (conventional antibiotics) to narrow (threoglucins). By modifying the chemical structure to include specific amino acid sequences and the 1,3-oxazinane heterocycle, the peptides achieve potent activity against S. suis at low concentrations (IC50 values in the low micromolar range) while maintaining no measurable toxicity to human cell lines even at higher concentrations

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If broad spectrum antibiotics are used, then multiple bacterial infections can be treated, but they cannot target specific bacteria without affecting other beneficial bacteria

Engineering Contradiction:

Improvebroad spectrum activityVSAvoidimpact on beneficial bacteria

Core Design Contradiction:

Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

The invention inverts the conventional approach by designing antibiotics with narrow rather than broad spectrum activity. Instead of attempting to create broad-spectrum agents that accidentally spare beneficial bacteria, threoglucins are specifically engineered to target only S. suis through their unique chemical structure, thereby inherently protecting the microbiome from disruption

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentUS20250025527A1Threoglucins as potent-antibacterial agents against streptococcus suis

Publication Date: 2025.01.23 THE TRUSTEES OF PRINCETON UNIV

AI summary

Compositions are provided that can be used to, e.g., treat or prevent infections caused by Streptococcus suis. The compositions may include one or more threoglucins in a carrier, at a total concentration of threoglucins being at least 1 μM. The at least one threoglucin may include one or more of threoglucins A-R. Such threoglucins may be produced by, e.g., growing a culture of Streptococcus suis in the presence of niacin, nicotinamide, and/or anabasine.