Modified beta-lactamases and methods and uses related thereto
The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects. Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.
1. A method for reducing the likelihood of a Clostridium difficile infection in a subject in need thereof, comprising administering an effective amount of a beta-lactamase to the subject, wherein:
the subject is receiving or will receive ceftriaxone; and
the beta-lactamase comprises an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 1 and an asparagine (N) or arginine (R) residue at a position corresponding to position 276 according to Ambler classification.
2. The method of claim 1 , wherein the Clostridium difficile infection is caused by unabsorbed ceftriaxone in the subject's intestinal tract.
3. The method of claim 1 , wherein the method maintains an ecological balance of normal intestinal microbiota.
4. The method of claim 1 , wherein the beta-lactamase comprises an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 1.
5. The method of claim 1 , wherein the beta-lactamase comprises an amino acid sequence having at least 99% sequence identity with SEQ ID NO: 1.
6. The method of claim 1 , wherein the beta-lactamase comprises the amino acid sequence of SEQ ID NO: 1.
7. The method of claim 1 , wherein the beta-lactamase is administered simultaneously to or sequentially with the ceftriaxone.
8. The method of claim 1 , wherein the ceftriaxone is administered intravenously.
9. A method for reducing the likelihood of a Clostridium difficile infection in a subject in need thereof, comprising administering an effective amount of a beta-lactamase to the subject, wherein:
the subject is receiving or will receive ceftriaxone; and
the beta-lactamase comprises the amino acid sequence of SEQ ID NO: 1 and an asparagine (N) residue at a position corresponding to position 276 according to Ambler classification.
10. The method of claim 9 , wherein the Clostridium difficile infection is caused by unabsorbed ceftriaxone in the subject's intestinal tract.
11. The method of claim 9 , wherein the method maintains an ecological balance of normal intestinal microbiota.
12. The method of claim 9 , wherein the beta-lactamase is administered simultaneously to or sequentially with the beta-lactam antibiotic.
13. The method of claim 9 , wherein the ceftriaxone is administered intravenously.