Efflux pumps as interventions to control infection caused by drug-resistance bacteria

2020 ◽  
Vol 25 (12) ◽  
pp. 2307-2316
Author(s):  
Nabeela Farhat ◽  
Abid Ali ◽  
Robert A. Bonomo ◽  
Asad U. Khan
Keyword(s):  
Drug Resistance ◽  
Efflux Pumps ◽  
Control Infection

scholarly journals Novel epitopes identified from efflux pumps ofMycobacterium tuberculosiscould induce cytotoxic T lymphocyte response

PeerJ ◽  
2015 ◽  
Vol 3 ◽  
pp. e1229 ◽  
Author(s):  
Ming-xia Zhai ◽  
Fei Chen ◽  
Yuan-yuan Zhao ◽  
Ya-hong Wu ◽  
Guo-dong Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Efflux Pump ◽  
Cytotoxic T Lymphocyte ◽  
Efflux Pumps ◽  
Common Mechanism ◽  
Antigenic Peptides ◽  
Ifn Γ ◽  
Cytotoxic T Lymphocyte Response

Overcoming drug-resistance is one of the major challenges to control tuberculosis (TB). The up-regulation of efflux pumps is one common mechanism that leads to drug-resistance. Therefore, immunotherapy targeting these efflux pump antigens could be promising strategy to be combined with current chemotherapy. Considering that CD8+ cytotoxic T lymphocytes (CTLs) induced by antigenic peptides (epitopes) could elicit HLA-restricted anti-TB immune response, efflux pumps from classical ABC family (Mycobacterium tuberculosis, Mtb) were chosen as target antigens to identify CTL epitopes. HLA-A2 restricted candidate peptides from Rv2937, Rv2686c and Rv2687c ofMycobacterium tuberculosiswere predicted, synthesized and tested. Five peptides could induce IFN-γ release and cytotoxic activity in PBMCs from HLA-A2+PPD+donors. Results from HLA-A2/Kbtransgenic mice immunization assay suggested that four peptides Rv2937-p168, Rv2937-p266, Rv2686c-p151, and Rv2686c-p181 could induce significant CTL responsein vivo. These results suggested that these novel epitopes could be used as immunotherapy candidates to TB drug-resistance.

58 Multi-drug resistance efflux pumps in bacteria: how they work?

2015 ◽  
Vol 33 (sup1) ◽  
pp. 39-39
Author(s):  
Melinda S. Wren ◽  
Kumkum Ganguli ◽  
Paige E. Paridington ◽  
Mira Dimitrijevic ◽  
Benjamin H. McMahon ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Efflux Pumps ◽  
Multi Drug Resistance

Efflux Pumps in Drug Resistance of Candida

2006 ◽  
Vol 6 (2) ◽  
pp. 69-83 ◽  
Author(s):  
R. Prasad ◽  
N. Gaur ◽  
M. Gaur ◽  
S. Komath
Keyword(s):  
Drug Resistance ◽  
Efflux Pumps

scholarly journals Targeting efflux pumps to overcome antifungal drug resistance

2016 ◽  
Vol 8 (12) ◽  
pp. 1485-1501 ◽  
Author(s):  
Ann R Holmes ◽  
Tony S Cardno ◽  
J Jacob Strouse ◽  
Irena Ivnitski-Steele ◽  
Mikhail V Keniya ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Efflux Pumps ◽  
Antifungal Drug ◽  
Antifungal Drug Resistance

scholarly journals Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences

2015 ◽  
Vol 35 (4) ◽  
Author(s):  
Ameena J. Haider ◽  
Megan H. Cox ◽  
Natalie Jones ◽  
Alice J. Goode ◽  
Katherine S. Bridge ◽  
...  
Keyword(s):  
Amino Acids ◽  
Drug Resistance ◽  
Protein Trafficking ◽  
Drug Transport ◽  
Protein Targeting ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Drug Efflux ◽  
Evolutionary Analysis ◽  
Drug Efflux Pump

Determining how efflux pumps function is important to understanding their role in drug resistance. We have identified amino acids in a human drug efflux pump that affect interaction with substrate and protein targeting.

scholarly journals The Contribution of Efflux Pumps in Mycobacterium abscessus Complex Resistance to Clarithromycin

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 153 ◽  
Author(s):  
Júlia S. Vianna ◽  
Diana Machado ◽  
Ivy B. Ramis ◽  
Fábia P. Silva ◽  
Dienefer V. Bierhals ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Mycobacterium Abscessus ◽  
New Drugs ◽  
Clarithromycin Resistance ◽  
Mycobacterium Abscessus Complex

The basis of drug resistance in Mycobacterium abscessus is still poorly understood. Nevertheless, as seen in other microorganisms, the efflux of antimicrobials may also play a role in M. abscessus drug resistance. Here, we investigated the role of efflux pumps in clarithromycin resistance using nine clinical isolates of M. abscessus complex belonging to the T28 erm(41) sequevar responsible for the inducible resistance to clarithromycin. The strains were characterized by drug susceptibility testing in the presence/absence of the efflux inhibitor verapamil and by genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. Efflux pump gene expression was studied by RT-qPCR upon exposure to clarithromycin. Verapamil increased the susceptibility to clarithromycin from 4- to ≥64-fold. The efflux pump genes MAB_3142 and MAB_1409 were found consistently overexpressed. The results obtained demonstrate that the T28 erm(41) polymorphism is not the sole cause of the inducible clarithromycin resistance in M. abscessus subsp. abscessus or bolletii with efflux activity providing a strong contribution to clarithromycin resistance. These data highlight the need for further studies on M. abscessus efflux response to antimicrobial stress in order to implement more effective therapeutic regimens and guidance in the development of new drugs against these bacteria.

scholarly journals Coordinate Hyperproduction of SmeZ and SmeJK Efflux Pumps Extends Drug Resistance in Stenotrophomonas maltophilia

2012 ◽  
Vol 57 (1) ◽  
pp. 655-657 ◽  
Author(s):  
Virginia C. Gould ◽  
Aki Okazaki ◽  
Matthew B. Avison
Keyword(s):  
Drug Resistance ◽  
Clinical Isolate ◽  
Clinical Relevance ◽  
Stenotrophomonas Maltophilia ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Content Type ◽  
Resistance Nodulation Division

ABSTRACTAStenotrophomonas maltophiliamutant that coordinately hyper-expresses three resistance nodulation division-type efflux pump genes,smeZ,smeJ, andsmeK, has been identified. SmeZ is responsible for elevating aminoglycoside MICs; SmeJ and SmeK are jointly responsible for elevating tetracycline, minocycline, and ciprofloxacin MICs and conferring levofloxacin resistance. One clinical isolate with this same phenotype was identified from a sample of six, and the isolate also coordinately hyper-expressessmeZandsmeJK, confirming the clinical relevance of our findings.

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