Composition and methods for disruption of bacterial biofilms without accompanying inflammation
View Patent ↗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.
1. A method for inhibiting, competing or titrating the binding of a deoxyribonucleic acid B II (DNABII) polypeptide to a microbial DNA in a biofilm, comprising contacting the microbial DNA in the biofilm with an effective amount of an isolated or recombinant polypeptide comprising a modified high mobility group-box 1 domain comprising C45S thereby inhibiting, competing or titrating the binding of the DNABII polypeptide to the microbial DNA.
2. The method of claim 1 , wherein the modified high mobility group-box 1 domain further comprises the substitutions C23S or C106S.
3. The method of claim 1 , wherein the contacting is in vitro or in vivo.
4. The method of claim 1 , wherein the biofilm is formed by Burkholderia cenocepacia, Enterobacter spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, Enterococcus faecium , Uropathogenic Escherichia coli (UPEC), Non-typeable Haemophilus influenzae (NTHI), or Aggregatibacter actinomycetemcomitans.
5. The method of claim 1 , wherein the contacting is in vivo in a subject and the method further comprises administering to the subject an effective amount of an antibiotic.
6. The method of claim 5 , wherein the subject is suffering from sepsis.