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Functional analysis of pneumococcal drug efflux pumps associates the MATE DinF transporter to quinolone susceptibility
- Source :
- Antimicrobial Agents and Chemotherapy; Vol 57
- Publication Year :
- 2013
-
Abstract
- The pneumococcal chromosome encodes about 140 transporters, many of which are predicted to be involved in efflux. In order to critically evaluate pneumococcal efflux, a series of transporter mutants were constructed, and their phenotypes were assayed by disk diffusion, microdilution drug susceptibility testing (MIC testing), growth of cultures at sub-MIC concentrations, and phenotype microarray analysis. Mutants with mutations in seven ATP binding cassette (ABC) transporters, three multiantimicrobial extrusion (MATE) family efflux pumps, and one major facilitator superfamily (MFS) transporter were obtained in Streptococcus pneumoniae strain DP1004. The susceptibility of these 11 mutants to over 250 different substances was compared to that of the parent strain. Of the tested transporters, only the ABC transporter PatAB (SP2073-5) presented a clear multidrug resistance (MDR) profile, as the mutant showed significantly increased susceptibility to ethidium bromide, acriflavine, and berberine. Among the other transporters analyzed, the mutants devoid of the MATE efflux pump SP2065 exhibited reduced susceptibility to novobiocin, and those with mutations of the MATE family DinF transport system (SP1939) exhibited increased susceptibility to moxifloxacin, ciprofloxacin, and levofloxacin. This change in quinolone MIC was found to be independent from the competence-mediated effect of quinolones on the cinA-recA-dinF operon. Furthermore, the dinF mutant, in contrast to the parental strain, allowed selection for quinolone-resistant mutants when exposed to moxifloxacin. These data confirm the clear MDR profile of the PatAB ABC transporter and suggest for the MATE DinF a phenotype associated with quinolone susceptibility, particularly for moxifloxacin.
- Subjects :
- medicine.drug_class
Mutant
ATP-binding cassette transporter
Quinolones
Microbiology
03 medical and health sciences
Bacterial Proteins
Mechanisms of Resistance
Disk Diffusion Antimicrobial Tests
Drug Resistance, Multiple, Bacterial
Operon
medicine
Pharmacology (medical)
030304 developmental biology
Pharmacology
0303 health sciences
drug resistance
biology
030306 microbiology
Membrane transport protein
Membrane Transport Proteins
Transporter
Quinolone
Major facilitator superfamily
Anti-Bacterial Agents
High-Throughput Screening Assays
3. Good health
Multiple drug resistance
Streptococcus pneumoniae
Infectious Diseases
Mutation
biology.protein
ATP-Binding Cassette Transporters
Efflux
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy; Vol 57
- Accession number :
- edsair.doi.dedup.....d5919d46b1f25bfb39101131049fb96b