Involvement of the CmeABC efflux pump in the macrolide resistance of Campylobacter coli

被引:61
作者
Cagliero, C [1 ]
Mouline, C [1 ]
Payot, S [1 ]
Cloeckaert, A [1 ]
机构
[1] INRA, UR086 Bioagresseurs, F-37380 Nouzilly, France
关键词
transporters; gene inactivation; mutations; 23S rRNA; ketolides;
D O I
10.1093/jac/dki292
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objectives: This study was conducted to examine the role of the CmeABC efflux pump in decreasing the susceptibility of Campylobacter coli to macrolides and ketolides in the context of absence or presence of mutations in the 23S rRNA genes. Methods: The cmeB gene was inactivated in strains of C. coli showing two different patterns of erythromycin resistance (low or high level of resistance) associated with the absence or presence of a A2075G mutation in the 23S rRNA genes. MICs of erythromycin, azithromycin, tylosin, telithromycin and ciprofloxacin were compared for wild-type (with or without efflux pump inhibitor) and mutant strains. Results: The cmeB gene inactivation (or addition of efflux pump inhibitor) led to the restoration of susceptibility of the low-level-resistant strains (no A2075G mutation in the 23S rRNA genes). In the highly resistant strains (A2075G mutation in the 23S rRNA genes), the MICs of erythromycin decreased 128- to 512-fold upon inactivation of the cmeB gene. MICs of azithromycin, tylosin and telithromycin were also affected by both addition of efflux pump inhibitor and cmeB gene inactivation, revealing these molecules as substrates of the CmeABC efflux pump. Compared with azithromycin, MICs of telithromycin drastically decreased upon cmeB gene inactivation even in the presence of a A2075G mutation in 23S rRNA genes. Conclusions: The CmeABC efflux pump acts synergically with 23S rRNA mutations to drastically increase the MICs of erythromycin and tylosin in C. coli. In contrast, azithromycin was less affected by efflux and telithromycin, although being a good substrate for the CmeABC efflux pump, was less affected by an A2075G mutation in 23S rRNA genes.
引用
收藏
页码:948 / 950
页数:3
相关论文
共 11 条
[1]   Campylobacter infection in 682 Bulgarian patients with acute enterocolitis, inflammatory bowel disease, and other chronic intestinal diseases [J].
Boyanova, L ;
Gergova, G ;
Spassova, Z ;
Koumanova, R ;
Yaneva, P ;
Mitov, I ;
Derejian, S ;
Krastev, Z .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2004, 49 (01) :71-74
[2]  
Franceschi F., 2004, Current Drug Targets - Infectious Disorders, V4, P177, DOI 10.2174/1568005043340740
[3]  
Lin J, 2005, CAMPYLOBACTER: MOLECULAR AND CELLULAR BIOLOGY, P205
[4]   A phenylalanine-arginine β-naphthylamide sensitive multidrug efflux pump involved in intrinsic and acquired resistance of Campylobacter to macrolides [J].
Mamelli, L ;
Amoros, JP ;
Pagès, JM ;
Bolla, JM .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2003, 22 (03) :237-241
[5]   Campylobacter [J].
Moore, JE ;
Corcoran, D ;
Dooley, JSG ;
Fanning, S ;
Lucey, B ;
Matsuda, M ;
McDowell, DA ;
Mégraud, F ;
Millar, BC ;
O'Mahony, R ;
O'Riordan, L ;
O'Rourke, M ;
Rao, JR ;
Rooney, PJ ;
Sails, A ;
Whyte, P .
VETERINARY RESEARCH, 2005, 36 (03) :351-382
[6]  
Padungton P, 2003, J VET MED SCI, V65, P161, DOI 10.1292/jvms.65.161
[7]   Selection and characterization of fluoroquinolone-resistant mutants of Campylobacter jejuni using enrofloxacin [J].
Payot, S ;
Cloeckaert, A ;
Chaslus-Dancla, E .
MICROBIAL DRUG RESISTANCE-MECHANISMS EPIDEMIOLOGY AND DISEASE, 2002, 8 (04) :335-343
[8]   Relative contribution of target gene mutation and efflux to fluoroquinolone and erythromycin resistance, in French poultry and pig isolates of Campylobacter coli [J].
Payot, S ;
Avrain, L ;
Magras, C ;
Praud, K ;
Cloeckaert, A ;
Chaslus-Dancla, E .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2004, 23 (05) :468-472
[9]   Increased erythromycin resistance in clinical Campylobacter in Northern Ireland -: an update [J].
Rao, D ;
Rao, JR ;
Crothers, E ;
McMullan, R ;
McDowell, D ;
McMahon, A ;
Rooney, PJ ;
Millar, BC ;
Moore, JE .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2005, 55 (03) :395-396
[10]  
Taylor DE, 2005, CAMPYLOBACTER: MOLECULAR AND CELLULAR BIOLOGY, P193