PMID- 31621139
OWN - NLM
STAT- MEDLINE
DCOM- 20200323
LR  - 20220412
IS  - 1365-2672 (Electronic)
IS  - 1364-5072 (Linking)
VI  - 128
IP  - 2
DP  - 2020 Feb
TI  - Sertraline as a promising antifungal agent: inhibition of growth and biofilm of 
      Candida auris with special focus on the mechanism of action in vitro.
PG  - 426-437
LID - 10.1111/jam.14490 [doi]
AB  - AIM: The aim of this present study was to investigate the antifungal mechanism of 
      sertraline against Candida auris (C. auris) and its effect on biofilm formation. 
      METHODS AND RESULTS: Sertraline, a repurposing drug with a history of human use 
      for the treatment of depression was screened against three different isolates of 
      C. auris, and was found to possess efficient antifungal activity. The antifungal 
      activity of sertraline was further confirmed by killing kinetics assay and 
      post-antifungal effect (PAFE). Sertraline inhibited C. auris yeast to hyphae 
      conversion and further the inhibition of biofilm formation showed 71% inhibition 
      upon treatment. Cell damage caused due to C. auris after treatment with 
      sertraline was observed using SEM and cell membrane damage was ascertained using 
      flow cytometry by Propidium Iodide (PI) uptake assay. The results of sorbitol 
      protection assay and ergosterol effect assay suggested that sertraline did not 
      affect the cell wall and did not act by binding to membrane ergosterol. The 
      mechanism of action of sertraline against C. auris was understood through in 
      silico docking studies that revealed the binding nature of sertraline to the 
      sterol 14 alpha demethylase which is involved in ergosterol biosynthesis. 
      Ergosterol that was quantified from treated cells showed a 5.5-fold decrease in 
      ergosterol production. CONCLUSION: Sertraline displayed promising antifungal 
      activity against C. auris involved in candidiasis infection and the mechanism of 
      action was predicted. SIGNIFICANCE AND IMPACT OF THIS STUDY: The results of this 
      study can encourage for the development of new antifungal agents and can be 
      promising antifungal agent against C. auris infection.
CI  - (c) 2019 The Society for Applied Microbiology.
FAU - Gowri, M
AU  - Gowri M
AD  - Department of Physics, Periyar University, Salem, Tamil Nadu, India.
FAU - Jayashree, B
AU  - Jayashree B
AD  - Department of Bioinformatics, Alagappa University, Karaikudi, India.
FAU - Jeyakanthan, J
AU  - Jeyakanthan J
AD  - Department of Bioinformatics, Alagappa University, Karaikudi, India.
FAU - Girija, E K
AU  - Girija EK
AUID- ORCID: 0000-0002-3528-2082
AD  - Department of Physics, Periyar University, Salem, Tamil Nadu, India.
LA  - eng
GR  - PDF/2016/003088/Department of Science and Technology, Ministry of Science and 
      Technology/
PT  - Journal Article
DEP - 20191113
PL  - England
TA  - J Appl Microbiol
JT  - Journal of applied microbiology
JID - 9706280
RN  - 0 (Antifungal Agents)
RN  - QUC7NX6WMB (Sertraline)
RN  - Z30RAY509F (Ergosterol)
SB  - IM
MH  - Antifungal Agents/*pharmacology
MH  - Biofilms/*drug effects
MH  - Candida/*drug effects/growth & development/physiology
MH  - Candidiasis/*microbiology
MH  - Ergosterol/metabolism
MH  - Humans
MH  - Microbial Sensitivity Tests
MH  - Sertraline/*pharmacology
OTO - NOTNLM
OT  - Candida auris
OT  - antifungal activity
OT  - biofilm
OT  - cell wall
OT  - ergosterol
OT  - induced fit docking
OT  - mechanism of action
OT  - sertraline
EDAT- 2019/10/18 06:00
MHDA- 2020/03/24 06:00
CRDT- 2019/10/18 06:00
PHST- 2019/05/24 00:00 [received]
PHST- 2019/09/27 00:00 [revised]
PHST- 2019/10/09 00:00 [accepted]
PHST- 2019/10/18 06:00 [pubmed]
PHST- 2020/03/24 06:00 [medline]
PHST- 2019/10/18 06:00 [entrez]
AID - 10.1111/jam.14490 [doi]
PST - ppublish
SO  - J Appl Microbiol. 2020 Feb;128(2):426-437. doi: 10.1111/jam.14490. Epub 2019 Nov 
      13.