Role of the multidrug efflux system MexXY in the emergence of moderate resistance to aminoglycosides among Pseudomonas aeruginosa isolates from patients with cystic fibrosis

被引:103
作者
Vogne, C
Aires, JR
Bailly, C
Hocquet, D
Plésiat, P
机构
[1] Hop Jean Minjoz, Bacteriol Lab, F-25030 Besancon, France
[2] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
关键词
D O I
10.1128/AAC.48.5.1676-1680.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
This study investigates the role of active efflux system MexXY in the emergence of aminoglycoside (AG) resistance among cystic fibrosis (CF) isolates of Pseudomonas aeruginosa. Three genotypically related susceptible and resistant (S/R) bacterial pairs and three other AG-resistant CF strains were compared to four non-CF strains moderately resistant to AGs. As demonstrated by immunoblot experiments, pump MexY was strongly overproduced in all of the resistant bacteria. This MexXY upregulation was associated with a 2- to 16-fold increase in the MICs of AGs in the S/R pairs and lower intracellullar accumulation of dihydrostreptomycin. Alterations in mexZ, the repressor gene of operon mexXY, were found in all of the AG-resistant CF isolates and in one non-CF strain. Complementation of these bacteria with a plasmid-borne mexZ gene dramatically reduced the MICs of AGs, thus highlighting the role played by MexXY in the development of moderate resistance in CF patients. In contrast, complementation of the three non-CF strains showing wild-type mexZ genes left residual levels of resistance to AGs. These data indicate that a locus different from mexZ may be involved in overproduction of MexXY and that other nonenzymatic mechanisms contribute to AG resistance in P. aeruginosa.
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页码:1676 / 1680
页数:5
相关论文
共 24 条
[1]   BASIC LOCAL ALIGNMENT SEARCH TOOL [J].
ALTSCHUL, SF ;
GISH, W ;
MILLER, W ;
MYERS, EW ;
LIPMAN, DJ .
JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (03) :403-410
[2]  
[Anonymous], 1991, MANUAL CLIN MICROBIO
[3]  
Ausubel F.M., 2000, CURRENT PROTOCOLS MO
[4]   Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis [J].
Barclay, ML ;
Begg, EJ ;
Chambers, ST ;
Thornley, PE ;
Pattemore, PK ;
Grimwood, K .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1996, 37 (06) :1155-1164
[5]  
Blázquez J, 2000, SCIENCE, V289, P392
[6]   A SIMPLE AND RAPID METHOD FOR THE PREPARATION OF GRAM-NEGATIVE BACTERIAL GENOMIC DNA [J].
CHEN, WP ;
KUO, TT .
NUCLEIC ACIDS RESEARCH, 1993, 21 (09) :2260-2260
[7]   ADAPTIVE RESISTANCE TO AMINOGLYCOSIDE ANTIBIOTICS FROM 1ST-EXPOSURE DOWN-REGULATION [J].
DAIKOS, GL ;
JACKSON, GG ;
LOLANS, VT ;
LIVERMORE, DM .
JOURNAL OF INFECTIOUS DISEASES, 1990, 162 (02) :414-420
[8]   HIGH-EFFICIENCY TRANSFORMATION OF ESCHERICHIA-COLI BY HIGH-VOLTAGE ELECTROPORATION [J].
DOWER, WJ ;
MILLER, JF ;
RAGSDALE, CW .
NUCLEIC ACIDS RESEARCH, 1988, 16 (13) :6127-6145
[9]   MexXY-OprM efflux pump is necessary for adaptive resistance of Pseudomonas aeruginosa to aminoglycosides [J].
Hocquet, D ;
Vogne, C ;
El Garch, F ;
Vejux, A ;
Gotoh, N ;
Lee, A ;
Lomovskaya, O ;
Plesiat, P .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (04) :1371-1375
[10]   Aminoglycoside efflux in Pseudomonas aeruginosa:: Involvement of novel outer membrane proteins [J].
Jo, JTH ;
Brinkman, FSL ;
Hancock, REW .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (03) :1101-1111