An important role of a "probable ATP-binding component of ABC transporter" during the process of Pseudomonas aeruginosa resistance to fluoroquinolone.
In order to find new drug target to eliminate the fluoroquinolone resistance, the in vitro progress of Pseudomonas aeruginosa fluoroquinolone resistance was mimicked, and then proteomic analysis was applied to comparing different protein profiles during the resistant process. The results show that the expression of a "probable ATP-binding component of ATP binding cassette (ABC) transporter" existed in ciprofloxacin-intermediate and -resistant strains, but not in sensitive strain. In addition, the ciprofloxacin concentrations in P. aeruginosa strains, which were obtained from the progress of P. aeruginosa fluoroquinolone resistance, were determined by means of HPLC; the results show that the decrease of the intracellular concentration of drug and the expression of this new protein nearly take place simultaneously. The changes of mRNA levels of the probable ATP-binding component of ABC transporter were detected by virtue of RT-PCR and showed that this protein did not express in the sensitive strains but expressed increasingly in the intermediate and resistant strains. In order to determine the relationships between the development of antibiotic resistance and this protein further, a DNAzyme was designed to aim at the mRNA of the probable ATP-binding component of ABC transporter directly; the ciprofloxacin resistance of P. aeruginosa was partially reduced in vivo by inhibiting the expression of this protein. This DNAzyme has no effect on sensitive strain. And the comparison of drug intracellular concentrations between DNAzyme-treated strains and its control strains shows that this protein may be included in the course of active drug efflux.
Zhou
Jinsong
J
The Third Hospital of Jilin University, Changchun, PR China. jinsongzhou@126.com
Hao
Dongyun
D
Wang
Xudong
X
Liu
Teimei
T
He
Chengyan
C
Xie
Feng
F
Sun
Yanhong
Y
Zhang
Jin
J
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001692:Biological Transport; D002939:Ciprofloxacin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000737:chemistry*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D040901:Proteomics / Q000379:methods*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D000255:Adenosine Triphosphate