Endolysins active against Bacillus bacteria, pharmaceutical compositions, and methods relating thereto
Inventors
Nelson, Daniel C. • Etobayeva, Irina V.
Assignees
US Department of Navy • University of Maryland College Park
Publication Number
US-11890330-B2
Publication Date
2024-02-06
Expiration Date
2039-05-16
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Abstract
The present invention relates to methods of treating or preventing a bacterial disease or infection, antibacterial compositions, and antibacterial surfaces, including an isolated polypeptide comprising an enzymatically active domain (EAD) of a Bacillus bacteriophage endolysin.
Core Innovation
The invention relates to methods of treating or preventing bacterial infections, antibacterial compositions, and antibacterial surfaces comprising isolated polypeptides that include enzymatically active domains (EADs) of Bacillus bacteriophage endolysins. These endolysins lyse the bacterial cell wall upon direct contact, including strains resistant to traditional antibiotics, making them suitable for biomedical and bioengineering applications.
The problem addressed is the difficulty in eliminating pathogenic Bacillus species, particularly members of the B. cereus sensu lato group, which are opportunistic pathogens and resilient to decontamination efforts. Bacillus species form resistant endospores that survive adverse conditions and persist on surfaces, contributing to infections and contamination in medical and food-processing environments. Traditional antibiotics face increasing resistance, thus alternatives like bacteriophage-encoded endolysins that can enzymatically degrade bacterial cell walls are needed.
The invention discloses nine families of Bacillus bacteriophage endolysins and, in particular, characterizes archetype lysins such as PlyP56, PlyN74, and PlyTB40, which possess relatively homologous cell wall binding domains (CBDs) and show high activity against Bacillus species including B. cereus. The endolysin polypeptides can be isolated, prepared recombinantly or synthetically, and used in pharmaceutical compositions or as antibacterial coatings on surfaces, including medical devices. Variants and chimeric combinations of EADs and CBDs are also disclosed to enhance or diversify therapeutic applications.
Claims Coverage
The patent contains one independent claim focused on a method of treating bacterial infection by administering specific isolated polypeptides, and dependent claims elaborating on compositions and combinations thereof. The main inventive features involve the use of Bacillus bacteriophage endolysin polypeptides and variants in therapeutic methods and compositions.
Use of isolated polypeptides comprising specific enzymatically active domains for treating bacterial infections
Administering to a subject a therapeutically effective amount of an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 3 or variants with at least about 90% identity thereto to treat bacterial infection.
Inclusion of cell wall binding domains in the isolated polypeptides
The isolated polypeptide further comprises an amino acid sequence of SEQ ID NO: 4, enhancing binding specificity to bacteria.
Concurrent or sequential administration of a secondary therapeutic agent
Administering a holin protein or one or more antibiotics in combination with the isolated endolysin polypeptide to enhance therapeutic efficacy.
Targeting infections caused by Bacillus strains
The method and compositions are specifically applicable to treating bacterial infections caused by Bacillus species.
The claims cover methods of treating bacterial infections using isolated endolysin polypeptides characterized by specific enzymatically active domains and binding domains, alone or in combination with other therapeutics, especially targeting Bacillus bacterial strains.
Stated Advantages
Endolysins lyse bacterial cell walls upon direct contact and are not inhibited by traditional antibiotic resistance mechanisms.
The disclosed endolysin polypeptides demonstrate particularly high activity against Bacillus species, including difficult-to-treat B. cereus species.
These endolysins can be used in various biomedical and bioengineering applications, including treating infections, antibacterial coatings on medical devices, and sanitizing agents for surfaces.
The enzymes maintain enzymatic activity over physiological pH and a broad temperature range, and can be engineered or combined to prolong therapeutic efficacy.
Documented Applications
Treating or preventing bacterial infections in humans and animals, particularly infections caused by Bacillus species including B. cereus and B. anthracis.
Use in pharmaceutical compositions for killing Gram-positive bacteria either alone or in combination with antibiotics or holin proteins.
Coatings on medical devices and implantable medical devices to provide antibacterial surfaces.
Sanitizing agents or disinfectants for dental and medical devices, hospital surfaces, food processing equipment, and other environments requiring bacterial contamination control.
Veterinary applications including treatment or prevention of bacterial infections and contamination in livestock, animal feed and equipment associated with animals.
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