scholarly journals Involvement of the SmeAB Multidrug Efflux Pump in Resistance to Plant Antimicrobials and Contribution to Nodulation Competitiveness in Sinorhizobium meliloti

2011 ◽  
Vol 77 (9) ◽  
pp. 2855-2862 ◽  
Author(s):  
Shima Eda ◽  
Hisayuki Mitsui ◽  
Kiwamu Minamisawa
Keyword(s):  
Antimicrobial Resistance ◽  
Sinorhizobium Meliloti ◽  
Efflux Pump ◽  
Major Facilitator Superfamily ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Content Type ◽  
Multidrug Efflux Pumps ◽  
Nodulation Competitiveness ◽  
Major Facilitator

ABSTRACTThe contributions of multicomponent-type multidrug efflux pumps to antimicrobial resistance and nodulation ability inSinorhizobium melilotiwere comprehensively analyzed. Computational searches identified genes in theS. melilotistrain 1021 genome encoding 1 pump from the ATP-binding cassette family, 3 pumps from the major facilitator superfamily, and 10 pumps from the resistance-nodulation-cell division family, and subsequently, these genes were deleted either individually or simultaneously. Antimicrobial susceptibility tests demonstrated that deletion of thesmeABpump genes resulted in increased susceptibility to a range of antibiotics, dyes, detergents, and plant-derived compounds and, further, that specific deletion of thesmeCDorsmeEFgenes in a ΔsmeABbackground caused a further increase in susceptibility to certain antibiotics. Competitive nodulation experiments revealed that thesmeABmutant was defective in competing with the wild-type strain for nodulation. The introduction of a plasmid carryingsmeABinto thesmeABmutant restored antimicrobial resistance and nodulation competitiveness. These findings suggest that the SmeAB pump, which is a major multidrug efflux system ofS. meliloti, plays an important role in nodulation competitiveness by mediating resistance toward antimicrobial compounds produced by the host plant.

scholarly journals Characterization of Posttranslationally Modified Multidrug Efflux Pumps Reveals an Unexpected Link between Glycosylation and Antimicrobial Resistance

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Sherif Abouelhadid ◽  
John Raynes ◽  
Tam Bui ◽  
Jon Cuccui ◽  
Brendan W. Wren
Keyword(s):  
Antimicrobial Resistance ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Gram Negative ◽  
Content Type ◽  
Multidrug Efflux Pumps ◽  
Pump Activity

ABSTRACT The substantial rise in multidrug-resistant bacterial infections is a current global imperative. Cumulative efforts to characterize antimicrobial resistance in bacteria has demonstrated the spread of six families of multidrug efflux pumps, of which resistance-nodulation-cell division (RND) is the major mechanism of multidrug resistance in Gram-negative bacteria. RND is composed of a tripartite protein assembly and confers resistance to a range of unrelated compounds. In the major enteric pathogen Campylobacter jejuni, the three protein components of RND are posttranslationally modified with N-linked glycans. The direct role of N-linked glycans in C. jejuni and other bacteria has long been elusive. Here, we present the first detailed account of the role of N-linked glycans and the link between N-glycosylation and antimicrobial resistance in C. jejuni. We demonstrate the multifunctional role of N-linked glycans in enhancing protein thermostability, stabilizing protein complexes and the promotion of protein-protein interaction, thus mediating antimicrobial resistance via enhancing multidrug efflux pump activity. This affirms that glycosylation is critical for multidrug efflux pump assembly. We present a generalized strategy that could be used to investigate general glycosylation system in Campylobacter genus and a potential target to develop antimicrobials against multidrug-resistant pathogens. IMPORTANCE Nearly all bacterial species have at least a single glycosylation system, but the direct effects of these posttranslational protein modifications are unresolved. Glycoproteome-wide analysis of several bacterial pathogens has revealed general glycan modifications of virulence factors and protein assemblies. Using Campylobacter jejuni as a model organism, we have studied the role of general N-linked glycans in the multidrug efflux pump commonly found in Gram-negative bacteria. We show, for the first time, the direct link between N-linked glycans and multidrug efflux pump activity. At the protein level, we demonstrate that N-linked glycans play a role in enhancing protein thermostability and mediating the assembly of the multidrug efflux pump to promote antimicrobial resistance, highlighting the importance of this posttranslational modification in bacterial physiology. Similar roles for glycans are expected to be found in other Gram-negative pathogens that possess general protein glycosylation systems.

scholarly journals The Varied Role of Efflux Pumps of the MFS Family in the Interplay of Bacteria with Animal and Plant Cells

2019 ◽  
Vol 7 (9) ◽  
pp. 285 ◽  
Author(s):  
Pasqua ◽  
Grossi ◽  
Zennaro ◽  
Fanelli ◽  
Micheli ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Major Facilitator Superfamily ◽  
Host Cells ◽  
Multidrug Efflux ◽  
Animal Cells ◽  
Multidrug Efflux Pumps ◽  
Wide Range ◽  
Major Facilitator

Efflux pumps represent an important and large group of transporter proteins found in all organisms. The importance of efflux pumps resides in their ability to extrude a wide range of antibiotics, resulting in the emergence of multidrug resistance in many bacteria. Besides antibiotics, multidrug efflux pumps can also extrude a large variety of compounds: Bacterial metabolites, plant-produced compounds, quorum-sensing molecules, and virulence factors. This versatility makes efflux pumps relevant players in interactions not only with other bacteria, but also with plant or animal cells. The multidrug efflux pumps belonging to the major facilitator superfamily (MFS) are widely distributed in microbial genomes and exhibit a large spectrum of substrate specificities. Multidrug MFS efflux pumps are present either as single-component transporters or as tripartite complexes. In this review, we will summarize how the multidrug MFS efflux pumps contribute to the interplay between bacteria and targeted host cells, with emphasis on their role in bacterial virulence, in the colonization of plant and animal host cells and in biofilm formation. We will also address the complexity of these interactions in the light of the underlying regulatory networks required for the effective activation of efflux pump genes.

scholarly journals Multiresistance Genes of Rhizobium etli CFN42

2000 ◽  
Vol 13 (5) ◽  
pp. 572-577 ◽  
Author(s):  
Ramón González-Pasayo ◽  
Esperanza Martínez-Romero
Keyword(s):  
Wild Type Strain ◽  
Efflux Pump ◽  
Rhizobium Etli ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Enhanced Sensitivity ◽  
Multidrug Efflux Pumps ◽  
High Concentrations ◽  
Major Facilitator

Multidrug efflux pumps of bacteria are involved in the resistance to various antibiotics and toxic compounds. In Rhizobium etli, a mutualistic symbiont of Phaseolus vulgaris (bean), genes resembling multidrug efflux pump genes were identified and designated rmrA and rmrB. rmrA was obtained after the screening of transposon-generated fusions that are inducible by bean-root released flavonoids. The predicted gene products of rmrAB shared significant homology to membrane fusion and major facilitator proteins, respectively. Mutants of rmrA formed on average 40% less nodules in bean, while mutants of rmrA and rmrB had enhanced sensitivity to phytoalexins, flavonoids, and salicylic acid, compared with the wild-type strain. Multidrug resistance genes emrAB from Escherichia coli complemented an rmrA mutant from R. etli for resistance to high concentrations of naringenin.

scholarly journals LmrS Is a Multidrug Efflux Pump of the Major Facilitator Superfamily from Staphylococcus aureus

2010 ◽  
Vol 54 (12) ◽  
pp. 5406-5412 ◽  
Author(s):  
Jody L. Floyd ◽  
Kenneth P. Smith ◽  
Sanath H. Kumar ◽  
Jared T. Floyd ◽  
Manuel F. Varela
Keyword(s):  
Staphylococcus Aureus ◽  
Efflux Pump ◽  
Sodium Dodecyl ◽  
Fold Increase ◽  
Relative Increase ◽  
Major Facilitator Superfamily ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Major Facilitator ◽  
Lincomycin Resistance

ABSTRACT A multidrug efflux pump designated LmrS (lincomycin resistance protein of Staphylococcus aureus), belonging to the major facilitator superfamily (MFS) of transporters, was cloned, and the role of LmrS in antimicrobial efflux was evaluated. The highest relative increase in MIC, 16-fold, was observed for linezolid and tetraphenylphosphonium chloride (TPCL), followed by an 8-fold increase for sodium dodecyl sulfate (SDS), trimethoprim, and chloramphenicol. LmrS has 14 predicted membrane-spanning domains and is homologous to putative lincomycin resistance proteins of Bacillus spp., Lactobacillus spp., and Listeria spp.

scholarly journals Structure of the periplasmic adaptor protein from a major facilitator superfamily (MFS) multidrug efflux pump

FEBS Letters ◽  
2014 ◽  
Vol 588 (17) ◽  
pp. 3147-3153 ◽  
Author(s):  
Philip Hinchliffe ◽  
Nicholas P. Greene ◽  
Neil G. Paterson ◽  
Allister Crow ◽  
Colin Hughes ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Adaptor Protein ◽  
Major Facilitator Superfamily ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Major Facilitator

scholarly journals Hypoxia Increases Antibiotic Resistance in Pseudomonas aeruginosa through Altering the Composition of Multidrug Efflux Pumps

2012 ◽  
Vol 56 (4) ◽  
pp. 2114-2118 ◽  
Author(s):  
Bettina Schaible ◽  
Cormac T. Taylor ◽  
Kirsten Schaffer
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Content Type ◽  
Hypoxic Conditions ◽  
Multidrug Efflux Pumps ◽  
The Impact

ABSTRACTAntibiotic resistance is a significant and developing problem in general medical practice and a common clinical complication in cystic fibrosis patients infected withPseudomonas aeruginosa. Such infections occur within hypoxic mucous deposits in the cystic fibrosis lung; however, little is known about how the hypoxic microenvironment influences pathogen behavior. Here we investigated the impact of hypoxia on antibiotic resistance inP. aeruginosa. The MICs of a selection of antibiotics were determined forP. aeruginosagrown under either normoxic or hypoxic conditions. The expression of mRNAs for resistance-nodulation-cell division (RND) multidrug efflux pump linker proteins was determined by real-time PCR, and multidrug efflux pump activity was inhibited using Phe-Arg β-naphthylamide dihydrochloride. The MIC values of a subset of clinically importantP. aeruginosaantibiotics were higher for bacteria incubated under hypoxia than under normoxia. Furthermore, hypoxia altered the stoichiometry of multidrug efflux pump linker protein subtype expression, and pharmacologic inhibition of these pumps reversed hypoxia-induced antibiotic resistance. We hypothesize that hypoxia increases multidrug resistance inP. aeruginosaby shifting multidrug efflux pump linker protein expression toward a dominance of MexEF-OprN. Thus, microenvironmental hypoxia may contribute significantly to the development of antibiotic resistance inP. aeruginosainfecting cystic fibrosis patients.

scholarly journals Antibiotic Susceptibility Profiles ofEscherichia coli Strains Lacking Multidrug Efflux Pump Genes

2001 ◽  
Vol 45 (4) ◽  
pp. 1126-1136 ◽  
Author(s):  
Mark C. Sulavik ◽  
Chad Houseweart ◽  
Christina Cramer ◽  
Nilofer Jiwani ◽  
Nicholas Murgolo ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Efflux Pump ◽  
Major Facilitator Superfamily ◽  
Multidrug Efflux ◽  
Intrinsic Resistance ◽  
Multidrug Efflux Pump ◽  
Gene Deletions ◽  
Small Multidrug Resistance ◽  
Major Facilitator ◽  
Susceptibility Profiles

ABSTRACT The contribution of seven known and nine predicted genes or operons associated with multidrug resistance to the susceptibility of Escherichia coli W3110 was assessed for 20 different classes of antimicrobial compounds that include antibiotics, antiseptics, detergents, and dyes. Strains were constructed with deletions for genes in the major facilitator superfamily, the resistance nodulation-cell division family, the small multidrug resistance family, the ATP-binding cassette family, and outer membrane factors. The agar dilution MICs of 35 compounds were determined for strains with deletions for multidrug resistance (MDR) pumps. Deletions in acrAB or tolC resulted in increased susceptibilities to the majority of compounds tested. The remaining MDR pump gene deletions resulted in increased susceptibilities to far fewer compounds. The results identify which MDR pumps contribute to intrinsic resistance under the conditions tested and supply practical information useful for designing sensitive assay strains for cell-based screening of antibacterial compounds.

scholarly journals Magnitude of Voriconazole Resistance in Clinical and Environmental Isolates of Aspergillus flavus and Investigation into the Role of Multidrug Efflux Pumps

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Raees A. Paul ◽  
Shivaprakash M. Rudramurthy ◽  
Manpreet Dhaliwal ◽  
Pankaj Singh ◽  
Anup K. Ghosh ◽  
...  
Keyword(s):  
Aspergillus Flavus ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Azole Resistance ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Environmental Isolates ◽  
Content Type ◽  
Multidrug Efflux Pumps

ABSTRACT The magnitude of azole resistance in Aspergillus flavus and its underlying mechanism is obscure. We evaluated the frequency of azole resistance in a collection of clinical (n = 121) and environmental isolates (n = 68) of A. flavus by the broth microdilution method. Six (5%) clinical isolates displayed voriconazole MIC greater than the epidemiological cutoff value. Two of these isolates with non-wild-type MIC were isolated from same patient and were genetically distinct, which was confirmed by amplified fragment length polymorphism analysis. Mutations associated with azole resistance were not present in the lanosterol 14-α demethylase coding genes (cyp51A, cyp51B, and cyp51C). Basal and voriconazole-induced expression of cyp51A homologs and various efflux pump genes was analyzed in three each of non-wild-type and wild-type isolates. All of the efflux pump genes screened showed low basal expression irrespective of the azole susceptibility of the isolate. However, the non-wild-type isolates demonstrated heterogeneous overexpression of many efflux pumps and the target enzyme coding genes in response to induction with voriconazole (1 μg/ml). The most distinctive observation was approximately 8- to 9-fold voriconazole-induced overexpression of an ortholog of the Candida albicans ATP binding cassette (ABC) multidrug efflux transporter, Cdr1, in two non-wild-type isolates compared to those in the reference strain A. flavus ATCC 204304 and other wild-type strains. Although the dominant marker of azole resistance in A. flavus is still elusive, the current study proposes the possible role of multidrug efflux pumps, especially that of Cdr1B overexpression, in contributing azole resistance in A. flavus.

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