Compositions and Methods for Treatment of Bacterial Infections

Abstract

A cell, isolated nucleic acid, vector, isolated polypeptide, and method of treating a bacterial infection are provided. The cell includes a modified Acinetobacter baumannii cell having a mutation in an A. baumannii gene selected from a mutation that occurs when generating mutations in A. baumannii using transposon mutagenesis. The isolated nucleic acid includes a sequence expressing a lpsB, mffT, or GctA polypeptide comprising at least one nucleic acid mutation. The vector includes the isolated nucleic acid. The isolated polypeptide includes a lpsB, mffT, or GctA polypeptide comprising at least one nucleic acid mutation. The method of treating a bacterial infection includes administering to a subject an effective amount of an Acinetobacter baumannii composition including modified Acinetobacter baumannii cell.

What is claimed is: 
     
         1 . A modified  Acinetobacter baumannii  cell having a mutation in an  A. baumannii  gene selected from a mutation that occurs when generating mutations in  A. baumannii  using transposon mutagenesis. 
     
     
         2 . The cell of  claim 1 , wherein the cell expresses a non-functional lpsB, mffT, or GctA polypeptide. 
     
     
         3 . The cell of  claim 1 , wherein the cell includes a mutation in lpsB, mffT, or GctA polypeptide. 
     
     
         4 . The cell of  claim 1 , wherein the cell is a killed cell. 
     
     
         5 . The cell of  claim 4 , wherein the cell is chemically-killed, disrupted, or heat-killed. 
     
     
         6 . The cell of  claim 1 , wherein the cell is a live cell. 
     
     
         7 . An isolated nucleic acid, comprising a sequence expressing a polypeptide having at least one nucleic acid mutation, the polypeptide being selected from the group consisting of lpsB, mffT, and GctA. 
     
     
         8 . The isolated nucleic acid of  claim 7 , wherein the isolated nucleic acid encodes a polypeptide having at least one nucleic acid mutation, the polypeptide being selected from the group consisting of lpsB, mffT, and GctA. 
     
     
         9 . A vector, comprising the isolated nucleic acid of  claim 7 . 
     
     
         10 . The vector of  claim 9 , wherein the isolated nucleic acid is operatively linked to an expression cassette. 
     
     
         11 . The vector of  claim 10 , wherein the expression cassette comprises a bacterial promoter. 
     
     
         12 . The vector of  claim 11 , wherein said promoter is an  Acinetobacter  promoter. 
     
     
         13 . An isolated polypeptide, comprising a polypeptide having at least one nucleic acid mutation, the polypeptide being selected from the group consisting of lpsB, mffT, and GctA. 
     
     
         14 . A method of treating a bacterial infection, comprising administering to a subject an effective amount of an  Acinetobacter baumannii  composition including a modified  Acinetobacter baumannii  cell according to  claim 1 . 
     
     
         15 . The method of  claim 14 , wherein the cell expresses a non-functional polypeptide selected from the group consisting of lpsB, mffT, and GctA. 
     
     
         16 . The method of  claim 14 , wherein the cell includes a mutation in a polypeptide selected from the group consisting of lpsB, mffT, and GctA. 
     
     
         17 . The method of  claim 14 , wherein the  Acinetobacter baumannii  composition comprises about 1×10 2  to about 1×10 8  modified  Acinetobacter baumannii  cells. 
     
     
         18 . The method of  claim 14 , wherein the cells are killed cells. 
     
     
         19 . The method of  claim 18 , wherein the cells are chemically-killed, disrupted, or heat-killed. 
     
     
         20 . The method of  claim 14 , wherein the cells are live cells. 
     
     
         21 . The method of  claim 14 , wherein the subject suffers from a respiratory infection, a urinary tract infection, meningitis, endocarditis, a wound infection, or bacteremia. 
     
     
         22 . The method of  claim 14 , further comprising administering an antibiotic to the subject. 
     
     
         23 . The method of  claim 22 , wherein the antibiotic is a polymyxin, a carbapenem, a tigecycline, a rifampin, or an aminoglycoside. 
     
     
         24 . The method of  claim 14 , wherein the subject has been diagnosed with a bacterial infection. 
     
     
         25 . The method of  claim 14 , wherein the subject is suspected of having a bacterial infection. 
     
     
         26 . The method of  claim 14 , wherein the bacterial infection is caused by a multi-drug or pan-drug resistant bacterium. 
     
     
         27 . The method of  claim 14 , wherein the bacterial infection is an  Acinetobacter  infection, a  Pseudomonas aeruginosa  infection, a  Burkholderia  infection, a  Klebsiella pneumoniae  infection, a  Stenotrophomonas maltophilia  infection, a  Haemophilus influenzae  infection, a  Staphylococcus aureus  infection, or a  Streptococcus pneumoniae  infection.