Mammalian Steroid Hormones Are Substrates for the Major RND- and MFS-Type Tripartite Multidrug Efflux Pumps of
            <i>Escherichia coli</i>

Elkins, Christopher A.; Mullis, Lisa B.

doi:10.1128/jb.188.3.1191-1195.2006

Cited by 64 publications

(54 citation statements)

References 24 publications

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“…The YhiUV efflux system relates to decreased susceptibility to steroids and erythromycin (7,19,20) and is under the control of EvgAS, the regulator of the two-component signal transduction system (14,20,21). Bohnert et al demonstrated the increased expression of yhiUV by qRT-PCR in two mutants of E. coli.…”

Section: Discussionmentioning

confidence: 99%

“…The overexpression of this pump often is associated with the MDR phenotype in E. coli (3,15,27,32). YhiUV is regulated by the EvgAS, the twocomponent system (20), and helps expel doxorubicin and erythromycin by cooperating with TolC (3,7,10,14,20,21). A previous report showed that a point mutation in yhiV, coding for YhiV, was associated with differences in the MDR phenotype (3).…”

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confidence: 99%

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Correlation of Overexpression of Efflux Pump Genes with Antibiotic Resistance inEscherichia coliStrains Clinically Isolated from Urinary Tract Infection Patients

et al. 2011

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Escherichia coli is one of the most common pathogens in urinary tract infections (UTIs), and antibiotic resistance in E. coli is becoming a serious problem in treating UTI. Efflux system overexpression is reported to contribute to E. coli resistance to several antibiotics. This study investigated the correlation of antibiotic susceptibilities with the overexpression of the efflux pump genes such as marA, yhiU, yhiV, and mdfA and with risk factors for antibiotic resistance in E. coli isolated from UTI patients. We examined the expression level of efflux pump genes using quantitative real-time reverse transcription-PCR (qRT-PCR). We also tested the in vitro susceptibilities to 12 kinds of antibiotics in 64 clinical strains of E. coli isolated from UTI patients. By multivariate analyses we revealed significant relationships between the overexpression of (i) marA and MICs of cefepime (FEP) and nalidixic acid (NAL), (ii) yhiV and MICs of minocycline (MIN), and (iii) mdfA and MICs of sitafloxacin (STX). In our investigation of the efflux pump genes, risk factors such as gender and the previous use of fluoroquinolones correlated with the overexpression of marA, and indwelling catheter use correlated with the overexpression of mdfA. In conclusion, we demonstrated that the increased expression of efflux pump genes such as marA and mdfA can lead to fluoroquinolone resistance in E. coli. These results contribute to our knowledge of the efflux system and raise the possibility of developing new agents, such as efflux pump inhibitors (EPIs), to antibiotic-resistant E. coli.There are many examples of multidrug resistance (MDR) in clinical isolates of Enterobacteriaceae, such as extended-spectrum ␤-lactamase (ESBL)-producing strains (6). The overexpression of efflux pumps was reported to contribute to MDR in E. coli (3,12). Almost all Gram-negative bacteria have genes for efflux pumps belonging to the resistance nodulation division (RND) family (3), and seven homologous RND-type pumps are known in E. coli. Five of these (AcrB, AcrF, MdtB, MdtC, and YhiV) are known to expel many kinds of drugs. Most of these efflux genes are not expressed or are expressed at low levels in clinical isolates (3). The tripartite efflux pump, AcrAB-TolC complex, contains AcrA, a fusion protein; AcrB, a cytoplasmic membrane transporter protein; and TolC, an outer membrane channel (12). The overexpression of this pump often is associated with the MDR phenotype in E. coli (3,15,27,32). YhiUV is regulated by the EvgAS, the twocomponent system (20), and helps expel doxorubicin and erythromycin by cooperating with TolC (3,7,10,14,20,21). A previous report showed that a point mutation in yhiV, coding for YhiV, was associated with differences in the MDR phenotype (3). The overexpression of efflux pump genes such as marA, yhiU, yhiV, and mdfA is related to antibiotic resistance, especially fluoroquinolones (3,12). This study investigated the relationship between the overexpression of these efflux pump genes and antibiotic resistance and risk factors for urin...

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Section: Discussionmentioning

confidence: 99%

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Correlation of Overexpression of Efflux Pump Genes with Antibiotic Resistance inEscherichia coliStrains Clinically Isolated from Urinary Tract Infection Patients

et al. 2011

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“…Other functions of this pump are participation in adherence, colonization and invasion of host cells [14]. AcrAB-TolC also could play a role in the transport of the calcium-channel components in the Escherichia coli membrane [46], might export hormones [26].…”

Section: Natural Functions Of Rnd Efflux Pumpsmentioning

confidence: 99%

Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

Wieczorek

Sacha²,

Hauschild³

et al. 2008

Folia Histochem Cytobiol.

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Abstract:Acinetobacter baumannii is an opportunistic pathogen which play the more and more greater role in the pathogenicity of the human. It is often attached with the hospital environment, in which is able easily to survive for many days even in adverse conditions. Acinetobacter baumannii is the species responsible for a serious nosocomial infections, especially in the intensive care units. Option of surviving in natural niches, and in the hospital environment could also be associated with the efflux pump mechanisms. Mechanisms of efflux universally appear in all cells (eukaryotic and prokaryotic) and play the physiological important role. In prokaryote, the main functions are evasion of such naturally produced molecules, removal of metabolic products and toxins. These pumps could also be involved in an early stage of infection, such as adhesion to host cells and the colonization. Importantly, they remove commonly used antibiotics from the cell in therapy of infections caused by these bacteria. Efflux pumps exemplify a unique phenomenon in drug resistance: a single mechanism causing resistance against several different classes of antibiotics. In Acinetobacter baumannii, the AdeABC efflux pump, a member of the resistance-nodulation-cell division family (RND), has been well characterized. Aminoglicosides, tetracyclines, erythromycin, chloramphenicol, trimethoprim, fluoroquinolones, some β-lactams, and also recently tigecycline, were found to be substrates for this pump. Drugs, as substrates for the AdeABC pump, can increase the expression of the AdeABC genes, leading to multidrug resistance (MDR). From this reason, treatment failure and death caused by Acinetobacter baumannii infections or underlying diseases are common. Because the AdeABC pump is widespread in Acinetobacter baumannii, similarly to other pumps in Gram-negative and Gram-positive bacteria, exists a need of searching a new therapeutic solutions. Specific efflux inhibitors of pumps (EPIs), including AdeABC inhibitors, could be suppress the activity of pumps and restore the sensitivity of such important bacteria as Acinetobacter baumannii to commonly used antibiotic.

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“…Our early analysis by using steroids as probes (37) showed that the diffusion across the OM bilayer is nearly 2 orders of magnitude slower than the diffusion across a typical phospholipid bilayer, such as the phospholipid bilayer that exists in the inner, cytoplasmic membrane. A recent study (11) suggested that this estimate likely needs to be adjusted somewhat downward. Nevertheless, the OM bilayer clearly functions as a formidable permeation barrier, because perturbing this bilayer results in a striking sensitization of Escherichia coli and Salmonella enterica serovar Typhimurium to various lipophilic inhibitors (44).…”

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PhoPQ-Mediated Regulation Produces a More Robust Permeability Barrier in the Outer Membrane ofSalmonella entericaSerovar Typhimurium

et al. 2007

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The PhoPQ two-component system of Salmonella enterica serovar Typhimurium produces a remodeling of the lipid A domain of the lipopolysaccharide, including the PagP-catalyzed addition of palmitoyl residue, the PmrAB-regulated addition of the cationic sugar 4-aminoarabinose and phosphoethanolamine, and the LpxOcatalyzed addition of a 2-OH group onto one of the fatty acids. By using the diffusion rates of the dyes ethidium, Nile red, and eosin Y across the outer membrane, as well as the susceptibility of cells to large, lipophilic agents, we evaluated the function of this membrane as a permeability barrier. We found that the remodeling process in PhoP-constitutive strains produces an outer membrane that serves as a very effective permeability barrier in an environment that is poor in divalent cations or that contains cationic peptides, whereas its absence in phoP null mutants produces an outer membrane severely compromised in its barrier function under these conditions. Removing combinations of the lipid A-remodeling functions from a PhoP-constitutive strain showed that the known modification reactions explain a major part of the PhoPQ-regulated changes in permeability. We believe that the increased barrier property of the remodeled bilayer is important in making the pathogen more resistant to the stresses that it encounters in the host, including attack by the cationic antimicrobial peptides. On the other hand, drug-induced killing assays suggest that the outer membrane containing unmodified lipid A may serve as a better barrier in the presence of high concentrations (e.g., 5 mM) of Mg 2؉ .Cells of gram-negative bacteria are surrounded by the outer membrane (OM), which functions primarily as a permeability barrier (35). Large, hydrophilic compounds are excluded by the narrow porin channels, and lipophilic compounds cross the unusual, asymmetric bilayer of this membrane only slowly. Our early analysis by using steroids as probes (37) showed that the diffusion across the OM bilayer is nearly 2 orders of magnitude slower than the diffusion across a typical phospholipid bilayer, such as the phospholipid bilayer that exists in the inner, cytoplasmic membrane. A recent study (11) suggested that this estimate likely needs to be adjusted somewhat downward. Nevertheless, the OM bilayer clearly functions as a formidable permeation barrier, because perturbing this bilayer results in a striking sensitization of Escherichia coli and Salmonella enterica serovar Typhimurium to various lipophilic inhibitors (44).One major factor that contributes to this barrier property is presumably the asymmetric structure of the OM bilayer, whose outer leaflet is composed nearly entirely of lipopolysaccharides (LPS) (25). (In fact, very low permeability was found in symmetric LPS bilayers assembled in the laboratory [40].) According to the lattice model for diffusion in liquids, a statistical average of rapidly fluctuating variable distances creates transient holes within the bilayer into which solutes can migrate (41). Thus, an effective memb...

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Mammalian Steroid Hormones Are Substrates for the Major RND- and MFS-Type Tripartite Multidrug Efflux Pumps of Escherichia coli

Cited by 64 publications

References 24 publications

Correlation of Overexpression of Efflux Pump Genes with Antibiotic Resistance inEscherichia coliStrains Clinically Isolated from Urinary Tract Infection Patients

Correlation of Overexpression of Efflux Pump Genes with Antibiotic Resistance inEscherichia coliStrains Clinically Isolated from Urinary Tract Infection Patients

Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

PhoPQ-Mediated Regulation Produces a More Robust Permeability Barrier in the Outer Membrane ofSalmonella entericaSerovar Typhimurium

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