Mechanisms of multidrug transporters

Bolhuis, Henk; Veen, Hendrik W van; Poolman, Bert; Driessen, Arnold J.M.; Konings, Wil N.

doi:10.1111/j.1574-6976.1997.tb00345.x

Cited by 159 publications

(59 citation statements)

References 199 publications

(258 reference statements)

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“…A large number of bacterial ABC-type drug export systems have been characterized (280). Most of these microbial drug extrusion systems are specific chemical or multidrug resistance (MDR) systems that remove various substances from the cytoplasm or membrane of a cell (281). Most of the currently known MDR systems use the PMF rather than ATP as the driving force and operate as drug/H ϩ antiporters (282).…”

Section: Detoxification Of Ros In Labmentioning

confidence: 99%

Stress Physiology of Lactic Acid Bacteria

Papadimitriou

Alegría

Bron

et al. 2016

Microbiol Mol Biol Rev

511

404

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SUMMARYLactic acid bacteria (LAB) are important starter, commensal, or pathogenic microorganisms. The stress physiology of LAB has been studied in depth for over 2 decades, fueled mostly by the technological implications of LAB robustness in the food industry. Survival of probiotic LAB in the host and the potential relatedness of LAB virulence to their stress resilience have intensified interest in the field. Thus, a wealth of information concerning stress responses exists today for strains as diverse as starter (e.g.,Lactococcus lactis), probiotic (e.g., severalLactobacillusspp.), and pathogenic (e.g.,EnterococcusandStreptococcusspp.) LAB. Here we present the state of the art for LAB stress behavior. We describe the multitude of stresses that LAB are confronted with, and we present the experimental context used to study the stress responses of LAB, focusing on adaptation, habituation, and cross-protection as well as on self-induced multistress resistance in stationary phase, biofilms, and dormancy. We also consider stress responses at the population and single-cell levels. Subsequently, we concentrate on the stress defense mechanisms that have been reported to date, grouping them according to their direct participation in preserving cell energy, defending macromolecules, and protecting the cell envelope. Stress-induced responses of probiotic LAB and commensal/pathogenic LAB are highlighted separately due to the complexity of the peculiar multistress conditions to which these bacteria are subjected in their hosts. Induction of prophages under environmental stresses is then discussed. Finally, we present systems-based strategies to characterize the “stressome” of LAB and to engineer new food-related and probiotic LAB with improved stress tolerance.

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Section: Detoxification Of Ros In Labmentioning

confidence: 99%

Stress Physiology of Lactic Acid Bacteria

Papadimitriou

Alegría

Bron

et al. 2016

Microbiol Mol Biol Rev

511

404

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“…The multidrug efflux pumps are membrane proteins that are involved in the extrusion of antibiotics and are classified into five families, including resistance-nodulation-division (RND), major facilitator superfamily (MFS), small multidrug resistance (SMR), ATP-binding cassette (ABC), and multidrug and toxic compound extrusion (MATE) (3). Of the five families, the RND-type efflux pumps form a tripartite assembly in the bacterial membrane, comprising an RND-type inner membrane protein (IMP), an outer membrane protein (OMP), and a membrane fusion protein (MFP) to link the IMP and OMP (4).…”

mentioning

confidence: 99%

The SmeYZ Efflux Pump of Stenotrophomonas maltophilia Contributes to Drug Resistance, Virulence-Related Characteristics, and Virulence in Mice

Lin

Huang²,

Chen

et al. 2015

Antimicrob Agents Chemother

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The resistance-nodulation-division (RND)-type efflux pump is one of the causes of the multidrug resistance of Stenotrophomonas maltophilia. The roles of the RND-type efflux pump in physiological functions and virulence, in addition to antibiotic extrusion, have attracted much attention. In this study, the contributions of the constitutively expressed SmeYZ efflux pump to drug resistance, virulence-related characteristics, and virulence were evaluated. S. maltophilia KJ is a clinical isolate of multidrug resistance. The smeYZ isogenic deletion mutant, KJ⌬YZ, was constructed by a gene replacement strategy. The antimicrobial susceptibility, virulence-related physiological characteristics, susceptibility to human serum and neutrophils, and in vivo virulence between KJ and KJ⌬YZ were comparatively assessed. The SmeYZ efflux pump contributed resistance to aminoglycosides and trimethoprim-sulfamethoxazole. Inactivation of smeYZ resulted in attenuation of oxidative stress susceptibility, swimming, flagella formation, biofilm formation, and secreted protease activity. Furthermore, loss of SmeYZ increased susceptibility to human serum and neutrophils and decreased in vivo virulence in a murine model. These findings suggest the possibility of attenuation of the resistance and virulence of S. maltophilia with inhibitors of the SmeYZ efflux pump.

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“…Two positively cooperative sites, with overlapping specificities, appear to be involved in drug binding and transport in P-glycoprotein [25], as well as in LmrA, a bacterial hemitransporter described below [26]. Drug extrusion from the inner leaflet of the membrane favors a 'hydrophobic vacuum cleaner' mechanism [8,27]. MDR1 P-glycoprotein is able to translocate the NBD derivatives of various lipids [9,28], but it remains to be seen whether normal phospholipids are indeed transported.…”

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confidence: 99%

Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters

Pietro

Conseil

Pérez‐Victoria

et al. 2002

CMLS, Cell. Mol. Life Sci.

228

168

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Cancer cell resistance to chemotherapy is often mediated by overexpression of P-glycoprotein, a plasma membrane ABC (ATP-binding cassette) transporter which extrudes cytotoxic drugs at the expense of ATP hydrolysis. P-glycoprotein (ABCB1, according to the human gene nomenclature committee) consists of two homologous halves each containing a transmembrane domain (TMD) involved in drug binding and efflux, and a cytosolic nucleotide-binding domain (NBD) involved in ATP binding and hydrolysis, with an overall (TMD-NBD)2 domain topology. Homologous ABC multidrug transporters, from the same ABCB family, are found in many species such as Plasmodiumfalciparum and Leishmania spp. protozoa, where they induce resistance to antiparasitic drugs. In yeasts, some ABC transporters involved in resistance to fungicides, such as Saccharomyces cerevisiae Pdr5p and Snq2p, display a different (NBD-TMD)2 domain topology and are classified in another family, ABCG. Much effort has been spent to modulate multidrug resistance in the different species by using specific inhibitors, but generally with little success due to additional cellular targets and/or extrusion of the potential inhibitors. This review shows that due to similarities in function and maybe in three-dimensional organization of the different transporters, common potential modulators have been found. An in vitro 'rational screening' was performed among the large flavonoid family using a four-step procedure: (i) direct binding to purified recombinant cytosolic NBD and/or full-length transporter, (ii) inhibition of ATP hydrolysis and energy-dependent drug interaction with transporter-enriched membranes, (iii) inhibition of cell transporter activity monitored by flow cytometry and (iv) chemosensitization of cell growth. The results indicate that prenylated flavonoids bind with high affinity, and strongly inhibit drug interaction and nucleotide hydrolysis. As such, they constitute promising potential modulators of multidrug resistance.

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Mechanisms of multidrug transporters

Cited by 159 publications

References 199 publications

Stress Physiology of Lactic Acid Bacteria

Stress Physiology of Lactic Acid Bacteria

The SmeYZ Efflux Pump of Stenotrophomonas maltophilia Contributes to Drug Resistance, Virulence-Related Characteristics, and Virulence in Mice

Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters

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