Modulation of bacterial membrane permeability
View Patent ↗Nucleic acids and polypeptides involved in regulation of membrane permeability in bacteria are disclosed. Also disclosed are methods of increasing sensitivity to antibiotics in multi-drug resistant bacteria by increasing expression of PprA or PprB proteins in bacterial cells, and methods for identifying compounds that modulate PprA/PprB expression.
1. A method of increasing sensitivity of an antibiotic resistant bacterium to an antibiotic comprising:
administering to an antibiotic resistant bacterium an isolated nucleic acid comprising the polynucleotide sequence of SEQ ID NO:1 and encoding a PprA polypeptide; and,
modulating in a bacterium expression of a PprA polypeptide; and,
increasing the membrane permeability of an antibiotic resistant bacterium; thereby,
increasing the sensitivity of an antibiotic resistant bacterium to an antibiotic.
2. The method of claim 1 , wherein the step of modulating levels of the PprA polypeptide comprises introducing into the antibiotic resistant bacterium a nucleic acid encoding the polypeptide.
3. The method of claim 2 , wherein the nucleic acid encodes an amino acid sequence identified by SEQ ID NO: 3.
4. The method of claim 1 , wherein the bacterium is a Pseudomonas aeruginosa bacterium.
5. The method of claim 1 , wherein the step results in a change in membrane permeability in the bacterium.
6. The method of claim 1 , wherein the antibiotic administered to the antibiotic resistant bacterium is an aminoglycoside.
7. A bacterium into which has been introduced a vector encoding a nucleic acid sequence identified by SEQ ID NO: 1 that modulates in the bacterium expression of a PprA polypeptide.
8. The bacterium of claim 7 , wherein the vector expresses the polypeptide identified by SEQ ID NO: 3.
9. The bacterium of claim 8 , wherein the polypeptide is PprA.
10. The bacterium of claim 7 , wherein the bacterium is a Pseudomonas aeruginosa bacterium.
11. A vector comprising a promoter operably linked to a nucleic acid encoding a PprA polypeptide.
12. The vector of claim 11 , wherein the nucleic acid comprises the polynucleotide sequence of SEQ ID NO:1.