Tigecycline resistance in Serratia marcescens associated with up-regulation of the SdeXY-HasF efflux system also active against ciprofloxacin and cefpirome.
OBJECTIVE
Efflux by RND-type transporters is known to confer resistance to tigecycline in several Enterobacteriaceae species and we examined the potential of this mechanism in Serratia marcescens using a clinical isolate and laboratory-selected mutants.


METHODS
Expression of RND-type efflux pump genes was analysed by real-time RT-PCR. Laboratory mutants were selected by exposure to either tigecycline or tetracycline in vitro. Efflux pump genes were inactivated by suicide plasmids containing the R6K gamma origin of replication.


RESULTS
Higher tigecycline MICs correlated with elevated expression of the RND-type efflux pump genes sdeXY. Inactivation of sdeY or the outer membrane component gene hasF reduced MICs of tigecycline, tetracycline, ciprofloxacin and cefpirome to below those for strain NCTC 10211. A tetracycline-selected laboratory mutant also showed increases in sdeXY expression and tigecycline MIC.


CONCLUSIONS
Up-regulation of endogenous SdeXY-HasF-mediated efflux is associated with tigecycline resistance in S. marcescens along with MIC rises for tetracycline, ciprofloxacin and cefpirome. Inactivation of this efflux system reduced MICs of those compounds to below those for strain NCTC 10211.
Hornsey
Michael
M
Antibiotic Resistance Monitoring and Reference Laboratory, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK. michael.hornsey@hpa.org.uk
Ellington
Matthew J
MJ
Doumith
Michel
M
Hudson
Sue
S
Livermore
David M
DM
Woodford
Neil
N
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000378:metabolism; D001693:Biological Transport, Active; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000378:metabolism / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D017353:Gene Deletion; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012641:Selection, Genetic; D016868:Serratia Infections / Q000382:microbiology; D012706:Serratia marcescens / Q000187:drug effects* / Q000302:isolation & purification; D000078304:Tigecycline; D015854:Up-Regulation; D000097572:Cefpirome
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D002939:Ciprofloxacin; D026901:Membrane Transport Proteins; D008911:Minocycline; D000078304:Tigecycline; D000097572:Cefpirome