scholarly journals Cooperation of the multidrug efflux pump and lipopolysaccharides in the intrinsic antibiotic resistance of Salmonella enterica serovar Typhimurium

2013 ◽  
Vol 68 (5) ◽  
pp. 1066-1070 ◽  
Author(s):  
Seiji Yamasaki ◽  
Saya Nagasawa ◽  
Aiko Fukushima ◽  
Mitsuko Hayashi-Nishino ◽  
Kunihiko Nishino
Keyword(s):  
Antibiotic Resistance ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Serovar Typhimurium

scholarly journals Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat

Microbiology ◽  
2011 ◽  
Vol 157 (3) ◽  
pp. 648-655 ◽  
Author(s):  
Eiji Nikaido ◽  
Ikue Shirosaka ◽  
Akihito Yamaguchi ◽  
Kunihiko Nishino
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Efflux Pump ◽  
Upstream Region ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Extracellular Signals ◽  
Multidrug Efflux Pumps ◽  
Serovar Typhimurium ◽  
Binding Sequence

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.

scholarly journals H-NS Modulates Multidrug Resistance of Salmonella enterica Serovar Typhimurium by Repressing Multidrug Efflux Genes acrEF

2009 ◽  
Vol 53 (8) ◽  
pp. 3541-3543 ◽  
Author(s):  
Kunihiko Nishino ◽  
Mitsuko Hayashi-Nishino ◽  
Akihito Yamaguchi
Keyword(s):  
Multidrug Resistance ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Serovar Typhimurium

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.

scholarly journals Evidence for an Efflux Pump Mediating Multiple Antibiotic Resistance in Salmonella enterica Serovar Typhimurium

2000 ◽  
Vol 44 (11) ◽  
pp. 3118-3121 ◽  
Author(s):  
Laura J. V. Piddock ◽  
David G. White ◽  
Karl Gensberg ◽  
Lilian Pumbwe ◽  
Deborah J. Griggs
Keyword(s):  
Antibiotic Resistance ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Efflux Pump ◽  
Northern Blotting ◽  
Multiple Antibiotic Resistance ◽  
Reverse Transcription Pcr ◽  
Carbonyl Cyanide ◽  
Serovar Typhimurium

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.

scholarly journals The ABC-Type Efflux Pump MacAB Protects Salmonella enterica serovar Typhimurium from Oxidative Stress

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Lydia M. Bogomolnaya ◽  
Katharine D. Andrews ◽  
Marissa Talamantes ◽  
Aimee Maple ◽  
Yury Ragoza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Salmonella Enterica ◽  
Efflux Pump ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Drug Efflux Pump

ABSTRACTMultidrug efflux pumps are integral membrane proteins known to actively excrete antibiotics. The macrolide-specific pump MacAB, the only ABC-type drug efflux pump inSalmonella, has previously been linked to virulence in mice. The molecular mechanism of this link betweenmacABand infection is unclear. We demonstrate thatmacABplays a role in the detoxification of reactive oxygen species (ROS), compounds that salmonellae are exposed to at various stages of infection.macABis induced upon exposure to H2O2and is critical for survival ofSalmonella entericaserovar Typhimurium in the presence of peroxide. Furthermore, we determined thatmacABis required for intracellular replication inside J774.A1 murine macrophages but is not required for survival in ROS-deficient J774.D9 macrophages.macABmutants also had reduced survival in the intestine in the mouse colitis model, a model characterized by a strong neutrophilic intestinal infiltrate where bacteria may experience the cytotoxic actions of ROS. Using an Amplex red-coupled assay,macABmutants appear to be unable to induce protection against exogenous H2O2in vitro, in contrast to the isogenic wild type. In mixed cultures, the presence of the wild-type organism, or media preconditioned by the growth of the wild-type organism, was sufficient to rescue themacABmutant from peroxide-mediated killing. Our data indicate that the MacAB drug efflux pump has functions beyond resistance to antibiotics and plays a role in the protection ofSalmonellaagainst oxidative stress. Intriguingly, our data also suggest the presence of a soluble anti-H2O2compound secreted bySalmonellacells through a MacAB-dependent mechanism.IMPORTANCEThe ABC-type multidrug efflux pump MacAB is known to be required forSalmonella entericaserovar Typhimurium virulence after oral infection in mice, yet the function of this pump during infection is unknown. We show that this pump is necessary for colonization of niches in infected mice where salmonellae encounter oxidative stress during infection. MacAB is required for growth in cultured macrophages that produce reactive oxygen species (ROS) but is not needed in macrophages that do not generate ROS. In addition, we show that MacAB is required to resist peroxide-mediated killingin vitroand for the inactivation of peroxide in the media. Finally, wild-type organisms, or supernatant from wild-type organisms grown in the presence of peroxide, rescue the growth defect ofmacABmutants in H2O2. MacAB appears to participate in the excretion of a compound that induces protection against ROS-mediated killing, revealing a new role for this multidrug efflux pump.

scholarly journals Correlation between the Antibiotic Resistance Genes and Susceptibility to Antibiotics among the Carbapenem-Resistant Gram-Negative Pathogens

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 255
Author(s):  
Salma M. Abdelaziz ◽  
Khaled M. Aboshanab ◽  
Ibrahim S. Yahia ◽  
Mahmoud A. Yassien ◽  
Nadia A. Hassouna
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Efflux Pump ◽  
Antibiotic Resistance Genes ◽  
Multiple Drug ◽  
P Value ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Gram Negative ◽  
Carbapenem Resistant

In this study, the correlation between the antibiotic resistance genes and antibiotic susceptibility among the carbapenem-resistant Gram-negative pathogens (CRGNPs) recovered from patients diagnosed with acute pneumonia in Egypt was found. A total of 194 isolates including Klebsiella pneumoniae (89; 46%), Escherichia coli (47; 24%) and Pseudomonas aeruginosa (58; 30%) were recovered. Of these, 34 (18%) isolates were multiple drug resistant (MDR) and carbapenem resistant. For the K. pneumoniae MDR isolates (n = 22), blaNDM (14; 64%) was the most prevalent carbapenemase, followed by blaOXA-48 (11; 50%) and blaVIM (4; 18%). A significant association (p value < 0.05) was observed between the multidrug efflux pump (AcrA) and resistance to β-lactams and the aminoglycoside acetyl transferase gene (aac-6’-Ib) gene and resistance to ciprofloxacin, azithromycin and β-lactams (except for aztreonam). For P. aeruginosa, a significant association was noticed between the presence of the blaSHV gene and the multidrug efflux pump (MexA) and resistance to fluoroquinolones, amikacin, tobramycin, co-trimoxazole and β-lactams and between the aac-6’-Ib gene and resistance to aminoglycosides. All P. aeruginosa isolates (100%) harbored the MexAB-OprM multidrug efflux pump while 86% of the K. pneumoniae isolates harbored the AcrAB-TolC pump. Our results are of great medical importance for the guidance of healthcare practitioners for effective antibiotic prescription.

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