Synergistic combination of duloxetine hydrochloride and fluconazole reduces the cell growth and capsule size of <i>Cryptococcus neoformans</i>

This study aimed to evaluate the effect of duloxetine hydrochloride (DH) on Cryptococcus neoformans. DH minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were 18.5 µg/mL, and the combination with fluconazole (FLZ) reduced the MIC value by 16-and 4-fold for DH and FLZ, respectively. The capsule size decreased by 67% and 16% when treated with DH and DH with FLZ, respectively. Therefore, this study showed that DH is active against C. neoformans alone and in combination with FLZ, leading to the reduction of the capsule size of this yeast.

Key words
Cryptococcus neoformans; capsule; fluconazole; duloxetine hydrochloride; synergistic combination

Authorship

RAQUEL T. MENEZES

Universidade Estadual Paulista (UNESP), Instituto de Ciência e Tecnologia, Departamento de Biociências e Diagnóstico Oral, Av. Engenheiro Francisco José Longo, 777, 12245-000 São José dos Campos, SP, BrazilUniversidade Estadual Paulista (UNESP)BrazilSão José dos Campos, SP, BrazilUniversidade Estadual Paulista (UNESP), Instituto de Ciência e Tecnologia, Departamento de Biociências e Diagnóstico Oral, Av. Engenheiro Francisco José Longo, 777, 12245-000 São José dos Campos, SP, Brazil

https://orcid.org/0000-0003-4250-5528

THAÍS C. PEREIRA

https://orcid.org/0000-0002-7206-3348

JULIANA C. JUNQUEIRA

https://orcid.org/0000-0001-6646-6856

LUCIANE D. OLIVEIRA

https://orcid.org/0000-0002-5465-9551

LILIANA SCORZONI

Pós-Graduação em Enfermagem, Universidade de Guarulhos (UNG), Rua Engenheiro Prestes Maia, 88, 07023-070 Guarulhos, SP, BrazilPós-Graduação em EnfermagemBrazilGuarulhos, SP, BrazilPós-Graduação em Enfermagem, Universidade de Guarulhos (UNG), Rua Engenheiro Prestes Maia, 88, 07023-070 Guarulhos, SP, Brazil

https://orcid.org/0000-0002-0178-6653

Correspondence to: Liliana Scorzoni E-mail: liliscorzoni@yahoo.com.br

AUTHOR CONTRIBUTIONS

Conceived and designed the experiments: RTM, TCP, LS. Performed the experiments: RTM, TCP. Analyzed the data: RTM, TCP, LS; Wrote the paper: RTM, TCP, JCJ, LDO, LS; Revised the paper: JCJ, LDO, LS.

SCIMAGO INSTITUTIONS RANKINGS

Figures | Tables

Figures (2)
Tables (1)

Thumbnail

Figure 1
Effect of treatment on capsule size of C. neoformans. a) DH at the minimal subinhibitory concentration (Sub-MIC) of 9.28 μg/mL. b) DH in concentrations equivalent to the synergistic value (treatments alone and in combination). Fifty cells were measured for each group. DH: duloxetine hydrochloride; FLZ: fluconazole; Control: C. neoformans ATCC H99 5 × 10⁶ cells /mL. (*): represents statistical difference in relation to the control (p < 0.05).

Thumbnail

Figure 2
Effect of DH on the polysaccharide capsule size of C. neoformans. C. neoformans cells were stained with Chinese ink and analyzed with a magnification of 400x. a) Control. b) DH at the minimal subinhibitory concentration (Sub-MIC) of 9.28 μg / mL. c) DH in synergistic concentrations (1.16 μg/mL and FLZ 1 μg /mL). DH: duloxetine hydrochloride; FLZ: fluconazole; Control: C. neoformans ATCC H99 5x10⁶ cells /mL.

Thumbnail

Table I
Susceptibility assay duloxetine hydrochloride (DH) alone or in combination with fluconazole against C. neoformans.

Figure 1 Effect of treatment on capsule size of C. neoformans. a) DH at the minimal subinhibitory concentration (Sub-MIC) of 9.28 μg/mL. b) DH in concentrations equivalent to the synergistic value (treatments alone and in combination). Fifty cells were measured for each group. DH: duloxetine hydrochloride; FLZ: fluconazole; Control: C. neoformans ATCC H99 5 × 10⁶ cells /mL. (*): represents statistical difference in relation to the control (p < 0.05).

Figure 2 Effect of DH on the polysaccharide capsule size of C. neoformans. C. neoformans cells were stained with Chinese ink and analyzed with a magnification of 400x. a) Control. b) DH at the minimal subinhibitory concentration (Sub-MIC) of 9.28 μg / mL. c) DH in synergistic concentrations (1.16 μg/mL and FLZ 1 μg /mL). DH: duloxetine hydrochloride; FLZ: fluconazole; Control: C. neoformans ATCC H99 5x10⁶ cells /mL.

Table I Susceptibility assay duloxetine hydrochloride (DH) alone or in combination with fluconazole against C. neoformans.

Susceptibility test (µg/mL)			Chequerboard assay		MIC reduction
Drug	MIC	MFC	MIC^co (CD and FLZ)	FICI (effect)	CD FLZ
CD	18.5	18.5	1.1 and 1	0.4891 (Syn)	16 x 4 x
FLZ	4	4

CD, Duloxetine hydrochloride; FLZ, fluconazole; MIC, minimum inhibitory concentration; MFC, minimum fungicial concentration; FICI, fractional inhibitory concentration; Syn, Synergistic; MIC^co, minimum inhibitory concentration in the combination.

How to cite

copy

Academia Brasileira de Ciências Rua Anfilófio de Carvalho, 29, 3º andar, 20030-060 Rio de Janeiro RJ Brasil, Tel: +55 21 3907-8100 - Rio de Janeiro - RJ - Brazil
E-mail: aabc@abc.org.br

Acompanhe os números deste periódico no seu leitor de RSS

Versão para download de PDF

PDF

Inglês

Versões e tradução automática

Versão original do texto

English

Tradução automática

Google Translator
Microsoft Translator

Como citar

RIS

BIBTEX

Outros formatos de citação e exportação:

SciELO - Scientific Electronic Library Online
Rua Dr. Diogo de Faria, 1087 – 9º andar – Vila Clementino 04037-003 São Paulo/SP - Brasil
E-mail: scielo@scielo.org

Leia a Declaração de Acesso Aberto

Métricas

Synergistic combination of duloxetine hydrochloride and fluconazole reduces the cell growth and capsule size of <i>Cryptococcus neoformans</i>

PlumX

Mensagem

[1] Correspondence to: Liliana Scorzoni E-mail: liliscorzoni@yahoo.com.br