scholarly journals CraA, a Major Facilitator Superfamily Efflux Pump Associated with Chloramphenicol Resistance in Acinetobacter baumannii

2009 ◽  
Vol 53 (9) ◽  
pp. 4013-4014 ◽  
Author(s):  
I. Roca ◽  
S. Marti ◽  
P. Espinal ◽  
P. Martínez ◽  
I. Gibert ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Major Facilitator Superfamily ◽  
Intrinsic Resistance ◽  
Chloramphenicol Resistance ◽  
Hospital Acquired Infections ◽  
Major Facilitator ◽  
Hospital Acquired

ABSTRACT Acinetobacter baumannii has been increasingly associated with hospital-acquired infections, and the presence of multidrug resistance strains is of great concern to clinicians. A. baumannii is thought to possess a great deal of intrinsic resistance to several antimicrobial agents, including chloramphenicol, although the mechanisms involved in such resistance are not well understood. In this work, we have identified a major facilitator superfamily efflux pump present in most A. baumannii strains, displaying strong substrate specificity toward chloramphenicol.

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 Two Distinct Major Facilitator Superfamily Drug Efflux Pumps Mediate Chloramphenicol Resistance in Streptomyces coelicolor

2009 ◽  
Vol 53 (11) ◽  
pp. 4673-4677 ◽  
Author(s):  
James J. Vecchione ◽  
Blair Alexander ◽  
Jason K. Sello
Keyword(s):  
Efflux Pump ◽  
Streptomyces Coelicolor ◽  
Efflux Pumps ◽  
Major Facilitator Superfamily ◽  
Close Relative ◽  
Gram Positive ◽  
Antibacterial Drugs ◽  
Chloramphenicol Resistance ◽  
Drug Activity ◽  
Major Facilitator

ABSTRACT Chloramphenicol, florfenicol, and thiamphenicol are used as antibacterial drugs in clinical and veterinary medicine. Two efflux pumps of the major facilitator superfamily encoded by the cmlR1 and cmlR2 genes mediate resistance to these antibiotics in Streptomyces coelicolor, a close relative of Mycobacterium tuberculosis. The transcription of both genes was observed by reverse transcription-PCR. Disruption of cmlR1 decreased the chloramphenicol MIC 1.6-fold, while disruption of cmlR2 lowered the MIC 16-fold. The chloramphenicol MIC of wild-type S. coelicolor decreased fourfold and eightfold in the presence of reserpine and Phe-Arg-β-naphthylamide, respectively. These compounds are known to potentiate the activity of some antibacterial drugs via efflux pump inhibition. While reserpine is known to potentiate drug activity against gram-positive bacteria, this is the first time that Phe-Arg-β-naphthylamide has been shown to potentiate drug activity against a gram-positive bacterium.

scholarly journals Structural and Functional Study of the Phenicol-Specific Efflux Pump FloR Belonging to the Major Facilitator Superfamily

2005 ◽  
Vol 49 (7) ◽  
pp. 2965-2971 ◽  
Author(s):  
Martine Braibant ◽  
Jacqueline Chevalier ◽  
Elisabeth Chaslus-Dancla ◽  
Jean-Marie Pagès ◽  
Axel Cloeckaert
Keyword(s):  
Efflux Pump ◽  
Major Facilitator Superfamily ◽  
Site Directed Mutagenesis ◽  
Functional Study ◽  
Efflux Transporters ◽  
Chloramphenicol Resistance ◽  
Active Efflux ◽  
Transmembrane Segments ◽  
Efflux Mechanism ◽  
Major Facilitator

ABSTRACT The florfenicol-chloramphenicol resistance gene floR from Salmonella enterica was previously identified and postulated to belong to the major facilitator (MF) superfamily of drug exporters. Here, we confirmed a computer-predicted transmembrane topological model of FloR, using the phoA gene fusion method, and classified this protein in the DHA12 family (containing 12 transmembrane domains) of MF efflux transporters. We also showed that FloR is a transporter specific for structurally associated phenicol drugs (chloramphenicol, florfenicol, thiamphenicol) which utilizes the proton motive force to energize an active efflux mechanism. By site-directed mutagenesis of specific charged residues belonging to putative transmembrane segments (TMS), two residues essential for active efflux function, D23 in TMS1 and R109 in TMS4, were identified. Of these, the acidic residue D23 seems to participate directly in the affinity pocket involved in phenicol derivative recognition. A third residue, E283 in TMS9, seems to be necessary for correct membrane folding of the transporter.

Tigecycline efflux in Acinetobacter baumannii is mediated by TetA in synergy with RND-type efflux transporters

2020 ◽  
Vol 75 (5) ◽  
pp. 1135-1139 ◽  
Author(s):  
Wuen Ee Foong ◽  
Jochen Wilhelm ◽  
Heng-Keat Tam ◽  
Klaas M Pos
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Gene Knockout ◽  
Drug Susceptibility ◽  
Major Facilitator Superfamily ◽  
Rt Pcr ◽  
E Coli ◽  
Rnd Efflux Pump ◽  
Major Facilitator

Abstract Objectives To investigate the role of Major Facilitator Superfamily (MFS)-type transporters from Acinetobacter baumannii AYE in tigecycline efflux. Methods Two putative tetracycline transporter genes of A. baumannii AYE (tetA and tetG) were heterologously expressed in Escherichia coli and drug susceptibility assays were conducted with tigecycline and three other tetracycline derivatives. The importance of TetA in tigecycline transport in A. baumannii was determined by complementation of tetA in WT and Resistance Nodulation cell Division (RND) gene knockout strains of A. baumannii ATCC 19606. Gene expression of the MFS-type tetA gene and RND efflux pump genes adeB, adeG and adeJ in A. baumannii AYE in the presence of tigecycline was analysed by quantitative real-time RT–PCR. Results Overproduction of TetA or TetG conferred resistance to doxycycline, minocycline and tetracycline in E. coli. Cells expressing tetA, but not those expressing tetG, conferred resistance to tigecycline, implying that TetA is a determinant for tigecycline transport. A. baumannii WT and RND-knockout strains complemented with plasmid-encoded tetA are significantly less susceptible to tigecycline compared with non-complemented strains. Efflux pump genes tetA and adeG are up-regulated in A. baumannii AYE in the presence of subinhibitory tigecycline concentrations. Conclusions TetA plays an important role in tigecycline efflux of A. baumannii by removing the drug from cytoplasm to periplasm and, subsequently, the RND-type transporters AdeABC and AdeIJK extrude tigecycline across the outer membrane. When challenged with tigecycline, tetA is up-regulated in A. baumannii AYE. Synergy between TetA and the RND-type transporters AdeABC and/or AdeIJK appears necessary for A. baumannii to confer higher tigecycline resistance via drug efflux.

scholarly journals AbuO, a TolC-Like Outer Membrane Protein of Acinetobacter baumannii, Is Involved in Antimicrobial and Oxidative Stress Resistance

2014 ◽  
Vol 59 (2) ◽  
pp. 1236-1245 ◽  
Author(s):  
Vijaya Bharathi Srinivasan ◽  
Vasanth Vaidyanathan ◽  
Govindan Rajamohan
Keyword(s):  
Oxidative Stress ◽  
Acinetobacter Baumannii ◽  
Outer Membrane ◽  
Efflux Pump ◽  
Outer Membrane Proteins ◽  
Major Facilitator Superfamily ◽  
Pcr Analysis ◽  
Content Type ◽  
Major Facilitator ◽  
And Oxidative Stress

ABSTRACTAlthoughAcinetobacter baumanniiis well accepted as a nosocomial pathogen, only a few of the outer membrane proteins (OMPs) have been functionally characterized. In this study, we demonstrate the biological functions of AbuO, a homolog of TolC fromEscherichia coli. Inactivation ofabuOled to increased sensitivity to high osmolarity and oxidative stress challenge. The ΔabuOmutant displayed increased susceptibility to antibiotics, such as amikacin, carbenicillin, ceftriaxone, meropenem, streptomycin, and tigecycline, and hospital-based disinfectants, such as benzalkonium chloride and chlorhexidine. The reverse transcription (RT)-PCR analysis indicated increased expression of efflux pumps (resistance nodulation cell division [RND] efflux pumpacrD, 8-fold; SMR-typeemrEhomolog, 12-fold; and major facilitator superfamily [MFS]-typeampGhomolog, 2.7-fold) and two-component response regulators (baeR, 4.67-fold;ompR, 10.43-fold) in the ΔabuOmutant together with downregulation ofrstA(4.22-fold) and the pilin chaperone (9-fold). The isogenic mutant displayed lower virulence in a nematode model (P< 0.01). Experimental evidence for the binding of MerR-type transcriptional regulator SoxR to radiolabeledabuOpromoter suggests regulation ofabuOby SoxR inA. baumannii.

scholarly journals Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p

2020 ◽  
Author(s):  
Yaojun Tong ◽  
Nuo Sun ◽  
Xiangming Wang ◽  
Qi Wei ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Multidrug Resistance ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Major Facilitator Superfamily ◽  
Drug Efflux ◽  
Multidrug Efflux Pump ◽  
Drug Efflux Pumps ◽  
Major Facilitator

AbstractClinical use of antimicrobials faces great challenges from the emergence of multidrug resistant (MDR) pathogens. The overexpression of drug efflux pumps is one of the major contributors to MDR. It is considered as a promising approach to overcome MDR by reversing the function of drug efflux pumps. In the life-threatening fungal pathogen Candida albicans, the major facilitator superfamily (MFS) transporter Mdr1p can excrete many structurally unrelated antifungals, leading to multidrug resistance. Here we report a counterintuitive case of reversing multidrug resistance in C. albicans by using a natural product berberine to hijack the overexpressed Mdr1p for its own importation. Moreover, we illustrate that the imported berberine accumulates in mitochondria, and compromises the mitochondrial function by impairing mitochondrial membrane potential and mitochondrial Complex I. It results in the selective elimination of Mdr1p overexpressed C. albicans cells. Furthermore, we show that berberine treatment can prolong the mean survival time (MST) of mice with a blood-borne dissemination of Mdr1p overexpressed multidrug resistant candidiasis. This study provided a potential direction of novel anti-MDR drug discovery by screening for multidrug efflux pump converters.

Membrane homoeostasis and multidrug resistance in yeast

2008 ◽  
Vol 28 (4) ◽  
pp. 217-228 ◽  
Author(s):  
Sneh Lata Panwar ◽  
Ritu Pasrija ◽  
Rajendra Prasad
Keyword(s):  
Multidrug Resistance ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Membrane Lipid ◽  
Major Facilitator Superfamily ◽  
Drug Efflux ◽  
Proper Functioning ◽  
Drug Efflux Pumps ◽  
Drug Efflux Pump ◽  
Major Facilitator

The development of MDR (multidrug resistance) in yeast is due to a number of mechanisms. The most documented mechanism is enhanced extrusion of drugs mediated by efflux pump proteins belonging to either the ABC (ATP-binding cassette) superfamily or MFS (major facilitator superfamily). These drug-efflux pump proteins are localized on the plasma membrane, and the milieu therein affects their proper functioning. Several recent studies demonstrate that fluctuations in membrane lipid composition affect the localization and proper functioning of the MDR efflux pump proteins. Interestingly, the efflux pumps of the ABC superfamily are particularly susceptible to imbalances in membrane-raft lipid constituents. This review focuses on the importance of the membrane environment in functioning of the drug-efflux pumps and explores a correlation between MDR and membrane lipid homoeostasis.

scholarly journals Bifunctional Enzyme SpoT Is Involved in Biofilm Formation ofHelicobacter pyloriwith Multidrug Resistance by Upregulating Efflux Pump Hp1174 (gluP)

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Xiaoran Ge ◽  
Yuying Cai ◽  
Zhenghong Chen ◽  
Sizhe Gao ◽  
Xiwen Geng ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Major Facilitator Superfamily ◽  
Bifunctional Enzyme ◽  
Content Type ◽  
H Pylori ◽  
Major Facilitator

ABSTRACTThe drug resistance ofHelicobacter pyloriis gradually becoming a serious problem. Biofilm formation is an important factor that leads to multidrug resistance (MDR) in bacteria. The ability ofH. pylorito form biofilms on the gastric mucosa is known. However, there are few studies on the regulatory mechanisms ofH. pyloribiofilm formation and multidrug resistance. Guanosine 3′-diphosphate 5′-triphosphate and guanosine 3′,5′-bispyrophosphate [(p)ppGpp] are global regulatory factors and are synthesized inH. pyloriby the bifunctional enzyme SpoT. It has been reported that (p)ppGpp is involved in the biofilm formation and multidrug resistance of various bacteria. In this study, we found that SpoT also plays an important role inH. pyloribiofilm formation and multidrug resistance. Therefore, it was necessary to carry out some further studies regarding its regulatory mechanism. Considering that efflux pumps are of great importance in the biofilm formation and multidrug resistance of bacteria, we tried to determine whether efflux pumps controlled by SpoT participate in these activities. We found that Hp1174 (glucose/galactose transporter [gluP]), an efflux pump of the major facilitator superfamily (MFS), is highly expressed in biofilm-forming and multidrug-resistant (MDR)H. pyloristrains and is upregulated by SpoT. Through further research, we determined thatgluPis involved inH. pyloribiofilm formation and multidrug resistance. Furthermore, the average expression level ofgluPin the clinical MDR strains (C-MDR) was considerably higher than that in the clinical drug-sensitive strains (C-DSS). Taken together, our results revealed a novel molecular mechanism ofH. pyloriresistance to multidrug exposure.

scholarly journals Roles of Efflux Pumps from Different Superfamilies in the Surface-Associated Motility and Virulence of Acinetobacter baumannii ATCC 17978

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
María Pérez-Varela ◽  
Jordi Corral ◽  
Jesús Aranda ◽  
Jordi Barbé
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Major Facilitator Superfamily ◽  
Content Type ◽  
Small Multidrug Resistance ◽  
Genes Encoding ◽  
Resistance Nodulation Division ◽  
Major Facilitator ◽  
Reported Data

ABSTRACT Although the relationship between Acinetobacter baumannii efflux pumps and antimicrobial resistance is well documented, less is known about the involvement of these proteins in the pathogenicity of this nosocomial pathogen. In previous work, we identified the AbaQ major facilitator superfamily (MFS) efflux pump and demonstrated its participation in the motility and virulence of A. baumannii. In the present study, we examined the role in these processes of A. baumannii transporters belonging to different superfamilies of efflux pumps. Genes encoding known or putative permeases belonging to efflux pump superfamilies other than the MFS were selected, and the corresponding knockouts were constructed. The antimicrobial susceptibilities of these mutants were consistent with previously reported data. In mutants of A. baumannii strain ATCC 17978 carrying inactivated genes encoding the efflux pumps A1S_2736 (resistance nodulation division [RND]), A1S_3371 (multidrug and toxic compound extrusion [MATE]), and A1S_0710 (small multidrug resistance [SMR]), as well as the newly described ATP-binding cassette (ABC) permeases A1S_1242 and A1S_2622, both surface-associated motility and virulence were reduced compared to the parental strain. However, inactivation of the genes encoding the known ABC permeases A1S_0536 and A1S_1535, the newly identified putative ABC permeases A1S_0027 and A1S_1057, or the proteobacterial antimicrobial compound efflux (PACE) transporters A1S_1503 and A1S_2063 had no effects on bacterial motility or virulence. Our results demonstrate the involvement of antimicrobial transporters belonging at least to five of the six known efflux pump superfamilies in both surface-associated motility and virulence in A. baumannii ATCC 17978.

scholarly journals ACINETOBACTER MAIN CAUSE OF HOSPITAL ACQUIRED INFECTIONS: A REVIEW

2017 ◽  
Vol 10 (5) ◽  
pp. 53
Author(s):  
Anania Arjuna
Keyword(s):  
Acinetobacter Baumannii ◽  
Medical Devices ◽  
Efflux Pump ◽  
Bloodstream Infections ◽  
Vital Role ◽  
Hospital Environment ◽  
Gram Negative ◽  
Hospital Acquired Infections ◽  
Tract Infections ◽  
Hospital Acquired

Hospital acquired infections (HAIs) are mostly caused by Gram-negative organisms and is one of the major issues in patient safety. These infectionsare often associated with the medical processes of hospitals such as invasive medical devices and various surgical procedures. Gram-negativeorganisms account for most infections in the hospital environment because of their ability to acquire resistant against multiple antibiotics. Throughdifferent mechanisms including the synthesis of β- lactamases, overexpression of transmembrane efflux pump, loss of porins, synthesis of antibiotic modifying enzymes, target mutations, ribosomal mutation or modifications, mutations in lipopolysaccharide structure etc. these organisms have developed drug-resistant property and the genes encoded in plasmids play a vital role in developing the resistant. Among all Gram-negative bacteria, Acinetobacter baumannii is an emerging pathogen that accounts for about 80% of all reported infections. Although other species of Acinetobacter are also often associated with HAIs. Acinetobacter is non-motile, obligate aerobic Gram-negative coccobacillus and are ubiquitous free-living saprophytes in soil and water. It is commonly transmitted through medical devices such as ventilators, urinary catheters and other invasive devices in hospitals but its ability to colonize on the skin of individuals often increases the rate of transmission through person to person contact. Patients admitted to Intensive Care Unit (ICU) are at the major risk of getting infected by A. baumannii and these includes pneumonia/ ventilator associated pneumonia(VAP), bloodstream infections, wound abscesses, urinary tract infections etc.Keywords: HAI, Acinetobacter baumannii, β- lactamases, VAP

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