Synthetic disugar hydrocarbons as natural analogs to control microbial behaviors
Inventors
Luk, Yan-Yeung • Wang, Guirong
Assignees
Syracuse University • Research Foundation of the State University of New York
Publication Number
US-11357786-B2
Publication Date
2022-06-14
Expiration Date
2035-04-03
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Abstract
Synthetic disaccharide hydrocarbons (DSHs) that reactive bacterials swarming motility and inhibit bacterial adhesion and biofilm formation. A library of DSHs were tested in several experiment for the impact on various Pseudomonas aeruginosa populations and compared against existing compounds to determine efficacy and utility. Certain DSHs were also to determine the ability to clear bacteria in a mouse pneumonia model.
Core Innovation
The invention introduces a class of synthetic disaccharide hydrocarbons (DSHs) that simulate and overpower the function of natural rhamnolipids secreted by Pseudomonas aeruginosa. These molecules can both promote swarming motility of Pseudomonas aeruginosa at low concentrations and inhibit swarming motility at high concentrations, dominating the effects produced by naturally occurring rhamnolipids. This dual-function capability allows precise control over microbial behaviors relevant to infectious disease processes.
The DSHs also exhibit significant effects on bacterial biofilms, notably inhibiting the formation of biofilms in various microbes such as E. coli, Pseudomonas aeruginosa, and Candida albicans with higher potency than natural rhamnolipids. Importantly, these compounds are able to disperse pre-formed biofilms, which natural rhamnolipids cannot achieve. As biofilms are the source of a large proportion of infectious diseases and are challenging to eradicate, this function of DSHs presents a promising approach for drug development and formulation.
This invention addresses the limitations in current anti-adhesion and anti-biofilm strategies by providing molecules that non-microbicidally control multiple bacterial behaviors, including swarming motility, adhesion, and biofilm formation and dispersion. The invention also demonstrates that DSHs do not inhibit bacterial growth at active concentrations, thereby reducing the potential for drug resistance development. Experimental evidence shows that selected DSHs clear bacteria in in vivo models, such as a mouse model of Pseudomonas aeruginosa pneumonia, and improve lung inflammation metrics compared to controls.
Claims Coverage
The patent claims one primary inventive feature focused on treating biofilm-related infections using a specific synthetic disaccharide hydrocarbon.
Treatment of Pseudomonas aeruginosa biofilm infections via dodecyl-β-maltoside
The invention provides a method for treating infections involving Pseudomonas aeruginosa bacteria forming a biofilm by administering an amount of dodecyl-β-maltoside (DβM) sufficient to disrupt rhamnolipids produced by the bacteria and disperse the biofilm. - The method specifically calls for DβM as the active agent to both disrupt rhamnolipid action and achieve biofilm dispersal. - The method is applicable to bacterial infections that are complications of cystic fibrosis. - Administration of DβM can be performed via a nebulizer. - The method optionally includes administering an effective amount of an antibiotic, which may also be delivered via a nebulizer. - Administration of DβM and antibiotic can be sequential or simultaneous.
The claim coverage centers on the administration of dodecyl-β-maltoside to disrupt and disperse Pseudomonas aeruginosa biofilms, particularly as a treatment for infections associated with cystic fibrosis, with defined administration routes and optional combinatory use with antibiotics.
Stated Advantages
DSHs exhibit control over multiple microbial behaviors, including swarming motility and biofilm formation, outperforming natural rhamnolipids.
DSHs can inhibit biofilm formation in a range of microbes, including E. coli, Pseudomonas aeruginosa, and Candida albicans, with higher potency than natural rhamnolipids.
DSHs disperse pre-formed biofilms, which natural rhamnolipids cannot accomplish.
These molecules are non-microbicidal at active concentrations, reducing the risk of invoking drug resistance.
DSHs demonstrated efficacy in clearing bacteria and improving lung inflammation in a mouse pneumonia model as compared to control.
Documented Applications
Treatment of infections involving Pseudomonas aeruginosa biofilms, especially in the context of cystic fibrosis.
Use of DSHs, including dodecyl-β-maltoside, via nebulizer or other inhalation devices for respiratory infections.
Application of DSHs in combination or sequentially with antibiotics to improve bacterial clearance in the lungs.
Application in treating medical conditions involving biofilm-forming bacterial pathogens, such as chronic wounds, C. difficile, cholera, and Crohn's disease.
Use in topical formulations, ingestible preparations, or endoscopic approaches for biofilm disruption on biotic and abiotic surfaces.
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