scholarly journals Efflux Pump Overexpression Contributes to Tigecycline Heteroresistance in Salmonella enterica serovar Typhimurium

Author(s):  
Yi Chen ◽  
Daxing Hu ◽  
Qijing Zhang ◽  
Xiao-Ping Liao ◽  
Ya-Hong Liu ◽  
...  
2006 ◽  
Vol 50 (1) ◽  
pp. 38-42 ◽  
Author(s):  
Vito Ricci ◽  
Peter Tzakas ◽  
Anthony Buckley ◽  
Nick C. Coldham ◽  
Laura J. V. Piddock

ABSTRACT It has been proposed that lack of a functional efflux system(s) will lead to a lower frequency of selection of resistance to fluoroquinolones and other antibiotics. We constructed five strains of Salmonella enterica serovar Typhimurium SL1344 that lacked efflux gene components of resistance nodulation cell division pumps (acrB, acrD, acrF, acrBacrF, and tolC) plus three strains that lack genes that effect efflux gene expression (marA, soxS, and ramA) and a hypermutable strain (mutS::aph). Strains were exposed to ciprofloxacin at 2× the MIC in agar, in the presence and absence of Phe-Arg-β-naphthylamide, an efflux pump inhibitor. Mutants were selected from all strains except those lacking acrB, tolC, or acrBacrF. For strains from which mutants were selected, there were no significant differences between the frequencies of resistance. Except for mutants of the ramA::aph strain, two phenotypes arose: resistance to quinolones only and multiple antibiotic resistance (MAR). ramA::aph mutants were resistant to quinolones only, suggesting a role for ramA in MAR in S. enterica serovar Typhimurium. Phe-Arg-β-naphthylamide (20 μg/ml) had no effect on the frequencies of resistance or ciprofloxacin MICs. In conclusion, functional AcrB and TolC in S. enterica serovar Typhimurium are important for the selection of ciprofloxacin-resistant mutants.


2000 ◽  
Vol 44 (11) ◽  
pp. 3118-3121 ◽  
Author(s):  
Laura J. V. Piddock ◽  
David G. White ◽  
Karl Gensberg ◽  
Lilian Pumbwe ◽  
Deborah J. Griggs

ABSTRACT The mechanism of multiple antibiotic resistance in six isolates ofSalmonella enterica serovar Typhimurium recovered from a patient treated with ciprofloxacin was studied to investigate the role of efflux in the resistance phenotype. Compared to the patient's pretherapy isolate (L3), five of six isolates accumulated less ciprofloxacin, three of six isolates accumulated less chloramphenicol, and all six accumulated less tetracycline. The accumulation of one or more antibiotics was increased by carbonyl cyanidem-chlorophenylhydrazone to concentrations similar to those accumulated by L3 for all isolates except one, in which accumulation of all three agents remained approximately half that of L3. All isolates had the published wild-type sequences of marO andmarR. No increased expression of marA,tolC, or soxS was observed by Northern blotting; however, three isolates showed increased expression ofacrB, which was confirmed by quantitative competitive reverse transcription-PCR. However, there were no mutations withinacrR or the promoter region of acrAB in any of the isolates.


Microbiology ◽  
2011 ◽  
Vol 157 (3) ◽  
pp. 648-655 ◽  
Author(s):  
Eiji Nikaido ◽  
Ikue Shirosaka ◽  
Akihito Yamaguchi ◽  
Kunihiko Nishino

Salmonella enterica serovar Typhimurium has at least nine multidrug efflux pumps. Among these, AcrAB is constitutively expressed and is the most efficient, playing a role in both drug resistance and virulence. The acrAB locus is induced by indole, Escherichia coli-conditioned medium, and bile salts. This induction is dependent on RamA through the binding sequence in the upstream region of acrA that binds RamA. In the present study, we made a detailed investigation of the ramA and acrAB induction mechanisms in Salmonella in response to indole, a biological oxidant for bacteria. We found that acrAB and ramA induction in response to indole is dependent on RamR. However, the cysteine residues of RamR do not play a role in the induction of ramA in response to indole, and the oxidative effect of indole is therefore not related to ramA induction via RamR. Furthermore, we showed that paraquat, a superoxide generator, induces acrAB but not ramA. We further discovered that the mechanism of acrAB induction in response to paraquat is dependent on SoxS. The data indicate that there are at least two independent induction pathways for acrAB in response to extracellular signals such as indole and paraquat. We propose that Salmonella utilizes these regulators for acrAB induction in response to extracellular signals in order to adapt itself to environmental conditions.


2011 ◽  
Vol 64 (6) ◽  
pp. 433-437 ◽  
Author(s):  
Seiji Yamasaki ◽  
Saya Nagasawa ◽  
Mitsuko Hayashi-Nishino ◽  
Akihito Yamaguchi ◽  
Kunihiko Nishino

2009 ◽  
Vol 53 (8) ◽  
pp. 3541-3543 ◽  
Author(s):  
Kunihiko Nishino ◽  
Mitsuko Hayashi-Nishino ◽  
Akihito Yamaguchi

ABSTRACT Screening of Salmonella mutants for the ability to increase β-lactam resistance has led to the identification of a mutation in hns, which codes for the histone-like nucleoid structuring protein (H-NS). In this study, we report that H-NS modulates multidrug resistance through repression of the genes that encode the AcrEF multidrug efflux pump in Salmonella enterica serovar Typhimurium.


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