Fungicidal action of geraniol against Candida albicans is potentiated by abrogated CaCdr1p drug efflux and fluconazole synergism

PloS One
Shweta SinghSaif Hameed

Abstract

Among the several mechanisms of multidrug resistance (MDR), overexpression of drug efflux pumps CaCdr1p and CaMdr1p belonging to ATP binding cassette (ABC) and major facilitator superfamily (MFS) respectively remain the predominant mechanisms of candidal infections. Therefore inhibiting or modulating the function of these transporters continues to draw attention as effective strategy to combat MDR. We have previously reported the antifungal potential of Geraniol (Ger), a natural monoterpenoid from Palmarosa oil, against Candida albicans. Herein, we explored the fungicidal nature of Ger. The Rhodamine 6G (R6G) and Nile red accumulation confirms the specific effect on CaCdr1p. Mechanistic insights with Candida cells overexpressing CaCdr1p and CaMdr1p revealed that Ger specifically modulates CaCdr1p activity. Kinetic studies further unraveled the competitive inhibition of Ger for R6G efflux as evident from increased apparent Km without affecting Vmax value. The effect of Ger on CaCdr1p was substantiated by molecular docking analyses, which depicted in-silico binding affinity of Ger with CaCdr1p and explored that Ger binds to the active site of CaCdr1p with higher binding energy. Although RT-PCR and western blot revealed no change ...Continue Reading

References

Jun 20, 1998·The Journal of Biological Chemistry·A DecottigniesA Goffeau
Feb 16, 2002·The EMBO Journal·M Cristina CruzJoseph Heitman
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
May 23, 2002·Antimicrobial Agents and Chemotherapy·Theodore C WhiteDavid A Stevens
Jun 21, 2002·Advances in Microbial Physiology·Rajendra Prasad Smriti
Jul 2, 2003·Journal of Biochemical and Biophysical Methods·Paiboon ReungpatthanaphongSamlee Mankhetkorn
Dec 11, 2003·Eukaryotic Cell·Suneet ShuklaRajendra Prasad
Mar 31, 2005·Biochemical and Biophysical Research Communications·Shogo YamamotoKohei Oda
Aug 27, 2005·The Journal of Antimicrobial Chemotherapy·Malcolm D Richardson
Jun 23, 2006·Infectious Disorders Drug Targets·R PrasadS S Komath
Jan 16, 2007·Clinical Microbiology Reviews·M A Pfaller, D J Diekema
Feb 6, 2007·PLoS Pathogens·Julia BregerEleftherios Mylonakis
May 28, 2009·Antimicrobial Agents and Chemotherapy·Monika SharmaRajendra Prasad
Apr 10, 2013·Journal of Ethnopharmacology·L N MisraFrancois Tchoumbougnang
Oct 29, 2013·International Journal of Microbiology·Saif Hameed, Zeeshan Fatima
Nov 22, 2013·PloS One·Lan-Xue ZhaoYuan-Ying Jiang
Aug 21, 2014·Interdisciplinary Perspectives on Infectious Diseases·Jyoti TanwarSaif Hameed
Sep 16, 2014·Frontiers in Pharmacology·Rajendra Prasad, Manpreet K Rawal
Apr 18, 2015·Nucleic Acids Research·Jianyi Yang, Yang Zhang
Aug 25, 2015·Frontiers in Microbiology·Izabela Ła̧ckaSławomir Milewski
Jul 10, 2016·Microbial Pathogenesis·Moiz A AnsariSaif Hameed
Sep 7, 2016·Revista Da Sociedade Brasileira De Medicina Tropical·Shweta SinghSaif Hameed
Jan 13, 2017·Journal of Peptide Science : an Official Publication of the European Peptide Society·Ersilia NigroAntonello Pessi
Jun 13, 2017·International Journal of Antimicrobial Agents·Joanna SzczepaniakAnna Krasowska
Aug 18, 2017·Infection and Drug Resistance·Elizabeth L Berkow, Shawn R Lockhart

❮ Previous
Next ❯

Citations

Oct 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maurine D'agostinoAnne Debourgogne
Mar 19, 2020·Current Pharmaceutical Design·Kleber Santiago SilvaMaristela Pereira
Nov 9, 2019·Scientific Reports·Rodrigo F M de AlmeidaRadosław Starosta
Mar 12, 2020·Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology]·Daniel Clemente de MoraesAntônio Ferreira-Pereira
Oct 18, 2020·International Journal of Molecular Sciences·Kamila Środa-PomianekAgata Kozioł
Jan 5, 2021·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Sandeep HansSaif Hameed
Feb 7, 2021·World Journal of Microbiology & Biotechnology·Fernando J ScariotSergio Echeverrigaray
Oct 26, 2020·Medical Mycology·Wafa RhimiClaudia Cafarchia
Jul 2, 2021·Applied Microbiology and Biotechnology·Payal GuptaKrishna Mohan Poluri
Aug 7, 2021·Pathogens·Rodrigo Rollin-PinheiroAntonio Ferreira-Pereira

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence microscopy
PCR
electrophoresis
filter disc
scraping
Fluorescence
confocal microscopy
Fluorescent microscopy

Software Mentioned

LOMET server
ChemBioDraw Office
Auto Dock Tools ( ADT )
TM
CASTp
TASSER
PyMOL
Autodock
Image J
MolProbity

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.

Biofilm & Infectious Disease

Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections.Here is the latest research on biofilm and infectious diseases.

Biofilms

Biofilms are adherent bacterial communities embedded in a polymer matrix and can cause persistent human infections that are highly resistant to antibiotics. Discover the latest research on Biofilms here.

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.