Banca de DEFESA: MICHAEL EDER DE OLIVEIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : MICHAEL EDER DE OLIVEIRA
DATE: 23/08/2022
TIME: 13:30
LOCAL: Campus Centro-Oeste - Sala 304 Bloco C
TITLE:

ASSESSMENT OF ISOLATE OR SYNERGIC ACTION USING ATORVASTATIN AND FLUCONAZOLE IN VITRO AND IN VIVO AGAINST AZO-RESISTANT Candida albicans FOR THE TREATMENT OF BIOFILMS AND INTRA-ABDOMINAL CANDIDIASIS

KEY WORDS:

Candida albicans, intra-abdominal candidiasis resistance, drug repositioning, statin.

PAGES: 155
BIG AREA: Ciências da Saúde
AREA: Saúde Coletiva
SUMMARY:

Among the pathogens caused by Candida albicans, intra-abdominal candidiasis (IAC) is the
most severe manifestation of this pathogen. However, the therapeutic arsenal is limited,
resistance is increasing, and there is low investment in research and development of drugs
of this category. Given this scenario, the repositioning of drugs can be considered an
important tool, as can already be observed for statins, which besides the known role in
reducing cholesterol levels, have already demonstrated action against C. albicans. In this
context, the aim of this study was to evaluate the action of atorvastatin alone or combined
with fluconazole against fluconazole-resistant C. albicans ATCC10231 in in vitro and in vivo
models. Previous results showed that atorvastatin has a minimal fungicidal concentration
(MIC) of 128 µg/mL against C. albicans, but when combined with fluconazole, the MIC of
atorvastatin was 0.25/0.01 µg/mL, while fluconazole (strain intrinsically resistant to this azol)
was 0.01 µg/mL. In view of these values, the other assays of the work were developed. In the
killing curve, the synergistic combination between atorvastatin and fluconazole showed
action with 24 hours of treatment. In the prevention of biofilm formation, none of the two
treatments were effective. In the pre-established biofilm, atorvastatin in the concentrations of
512 µg/mL and 256 µg/mL alone showed a reduction of biofilm of about 25% and 20%,
respectively. In the synergic treatment, the concentrations (the first value referring to
atorvastatin and the second to fluconazole) from 32/1,28 µg/mL to 8/0,32 µg/mL showed a
reduction of around 50% in biofilm. In the in vivo model, using swiss mice aged 6 to 8 weeks,
immunosuppressed with dexamethasone and infected with C. albicans ATCC10231 the
treatment with atorvastatin alone showed a greater reduction of C. albicans in the liver, while
the spleen showed a greater reduction of colonies with the synergistic treatment. The
difference between the two organs may be related to the tropism of atorvastatin by the liver
and its anti-inflammatory action by regulating TNF-α via NF-. Regarding the dosage of
cytokines, the increase of IL-17 in the spleen treated alone with fluconazole is noteworthy.
This is because IL-17 is produced in response to the presence of mannans (present in the
wall of C. albicans). The survival curve showed that the animals treated synergistically ended
the observational period in greater numbers with improvements in clinical signs. This
demonstrates that drug repositioning has the potential to act as an important tool in the
search for new antifungal protocols, mainly due to the low R&D investment in this area and
emergence of new strains resistant to available treatments.

BANKING MEMBERS:
Externa ao Programa - 1741307 - ADRIANA CRISTINA SOARES DE SOUZA
Externo à Instituição - ADRIANO GUIMARAES PARREIRA - UEMG
Externo à Instituição - FELIPE ROCHA DA SILVA SANTOS - UFMG
Presidente - 1742677 - JAQUELINE MARIA SIQUEIRA FERREIRA
Externa ao Programa - 1581671 - MAGNA CRISTINA DE PAIVA