PMID- 36830117
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230228
IS  - 2079-6382 (Print)
IS  - 2079-6382 (Electronic)
IS  - 2079-6382 (Linking)
VI  - 12
IP  - 2
DP  - 2023 Jan 18
TI  - Exposure of Paracoccidioides brasiliensis to Mebendazole Leads to Inhibition of 
      Fungal Energy Production.
LID - 10.3390/antibiotics12020206 [doi]
LID - 206
AB  - Paracoccidioidomycosis (PCM) is a fungal disease caused by organisms of the genus 
      Paracoccidioides spp. The treatment of the disease is lengthy and includes 
      several adverse effects. Various methodologies focus on the search for new 
      treatments against fungal disease, including the repositioning of drugs. Our 
      group showed the fungicidal effect of mebendazole in P. brasiliensis cells. Thus, 
      understanding the effect of exposing fungal cells to mebendazole is significant 
      for further studies in order to demonstrate it as a potential drug for the 
      treatment of PCM. A proteomic analysis of P. brasiliensis exposed to mebendazole 
      was carried out. Analyses showed that exposure strongly affected the pathways 
      related to energy production, such as glycolysis, fermentation, and the electron 
      transport chain. The quantification of adenosine triphosphate (ATP) and 
      mitochondrial activity demonstrated that the drug alters the electron chain, 
      resulting in an increase in oxidative stress. Enzymes such as superoxide 
      dismutase (SOD) and cytochrome c oxidase (Cyt C) were repressed in cells exposed 
      to mebendazole. The concentration of ethanol produced by the cells under 
      treatment demonstrated that the attempt to produce energy through fermentation is 
      also arrested. Thus, the drug inhibits fungal growth through changes in energy 
      metabolism, making it a promising compound for use in the treatment of PCM.
FAU - Rocha, Olivia Basso
AU  - Rocha OB
AUID- ORCID: 0000-0002-2094-6042
AD  - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal 
      University of Goias, Goiania 74690-900, Brazil.
FAU - E Silva, Kleber Santiago Freitas
AU  - E Silva KSF
AUID- ORCID: 0000-0001-5350-7313
AD  - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal 
      University of Goias, Goiania 74690-900, Brazil.
FAU - Moraes, Dayane
AU  - Moraes D
AUID- ORCID: 0000-0002-1031-1465
AD  - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal 
      University of Goias, Goiania 74690-900, Brazil.
FAU - Borges, Clayton Luiz
AU  - Borges CL
AUID- ORCID: 0000-0002-9914-8771
AD  - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal 
      University of Goias, Goiania 74690-900, Brazil.
FAU - Soares, Celia Maria de Almeida
AU  - Soares CMA
AUID- ORCID: 0000-0001-5378-9840
AD  - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal 
      University of Goias, Goiania 74690-900, Brazil.
FAU - Pereira, Maristela
AU  - Pereira M
AUID- ORCID: 0000-0002-5482-8036
AD  - Laboratory of Molecular Biology, Institute of Biological Sciences, Federal 
      University of Goias, Goiania 74690-900, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20230118
PL  - Switzerland
TA  - Antibiotics (Basel)
JT  - Antibiotics (Basel, Switzerland)
JID - 101637404
PMC - PMC9951877
OTO - NOTNLM
OT  - paracoccidioidomycosis
OT  - proteomics
OT  - repositioning
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/26 06:00
MHDA- 2023/02/26 06:01
PMCR- 2023/01/18
CRDT- 2023/02/25 01:12
PHST- 2022/12/28 00:00 [received]
PHST- 2023/01/14 00:00 [revised]
PHST- 2023/01/16 00:00 [accepted]
PHST- 2023/02/25 01:12 [entrez]
PHST- 2023/02/26 06:00 [pubmed]
PHST- 2023/02/26 06:01 [medline]
PHST- 2023/01/18 00:00 [pmc-release]
AID - antibiotics12020206 [pii]
AID - antibiotics-12-00206 [pii]
AID - 10.3390/antibiotics12020206 [doi]
PST - epublish
SO  - Antibiotics (Basel). 2023 Jan 18;12(2):206. doi: 10.3390/antibiotics12020206.