Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

被引：16

作者：

do Amaral Valente Sa, Livia Gurgel ^{[1
,2
]}

da Silva, Cecilia Rocha ^{[1
,2
]}

de Andrade Neto, Joao Batista ^{[1
,2
]}

Stefany Aires do Nascimento, Francisca Bruna ^{[1
,2
]}

Dias Barrosoi, Fatima Daiana ^{[1
,2
]}

da Silva, Lisandra Juvencio ^{[1
,2
]}

de Farias Cabral, Vitoria Pessoa ^{[1
,2
]}

Barbosa, Amanda Dias ^{[1
,2
]}

Silva, Jacilene ^{[3
]}

Marinho, Emmanuel Silva ^{[3
]}

de Moraes, Manoel Odorico ^{[4
]}

Franca Rios, Maria Erivanda ^{[2
]}

Cavalcanti, Bruno Coelho ^{[2
]}

Pampolha Lima, Iri Sandro ^{[5
]}

Nobre, Helio Vitoriano, Jr. ^{[2
]}

机构：

[1] Univ Fed Ceara, Sch Pharm, Dept Clin & Toxicol Anal, Lab Bioprospect Antimicrobial Mol LABIMAN, BR-60430170 Fortaleza, Ceara, Brazil

[2] Univ Fed Ceara, Drug Res & Dev Ctr, BR-60430275 Fortaleza, Ceara, Brazil

[3] Univ Estadual Ceara, Dept Chem, Grp Theoret Chem & Electrochem GQTE, BR-62930000 Limoeiro Do Norte, CE, Brazil

[4] Univ Fed Ceara, Dept Physiol & Pharmacol, Neuropharmacol Lab, BR-60430275 Fortaleza, Ceara, Brazil

[5] Univ Fed Ceara, Sch Med, Dept Pharmacol, BR-63048080 Barbalha, CE, Brazil

来源：

JOURNAL OF MEDICAL MICROBIOLOGY | 2020年 / 69卷 / 10期

关键词：

ALS3; antifungal activity; biofilm; Candida spp; etomidate; molecular docking; ALBICANS; UPDATE;

D O I：

10.1099/jmm.0.001241

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

This study evaluated the effect of etomidate against biofilms of Candida spp. and analysed through molecular docking the interaction of this drug with ALS3, an important protein for fungal adhesion. Three fluconazole-resistant fungi were used: Candida albicans, Candida parapsilosis and Candida tropicalis. Growing biofilms were exposed to etomidate at 31.25-500 mu g ml(-1). Then, an ALS3 adhesive protein from C. albicans was analysed through a molecular mapping technique, composed of a sequence of algorithms to perform molecular mapping simulation based on classic force field theory. Etomidate showed antifungal activity against growing biofilms of resistant C. albicans, C. parapsilosis and C. tropicalis at all concentrations used in the study. The etomidate coupling analysis revealed three interactions with the residues of interest compared to hepta-threonine, which remained at the ALS3 site. In addition, etomidate decreased the expression of mannoproteins on the surface of C. albicans. These results revealed that etomidate inhibited the growth of biofilms.

引用

页码：1221 / 1227

页数：7

共 32 条

[1] Virulence factors of Candida albicans [J].

Calderone, RA ;

Fonzi, WA .

TRENDS IN MICROBIOLOGY, 2001, 9 (07) :327-335

[2] Trichosporon inkin biofilms produce extracellular proteases and exhibit resistance to antifungals [J].

Cordeiro, Rossana de Aguiar ;

Serpa, Rosana ;

Uchoa Alexandre, Camila Flavia ;

de Farias Marques, Francisca Jakelyne ;

Silva de Melo, Charlline Vladia ;

Franco, Jonatas da Silva ;

de Jesus Evangelista, Antonio Jose ;

de Camargo, Zoilo Fires ;

Nogueira Brilhante, Raimunda Samia ;

Gadelha Rocha, Marcos Fabio ;

Bezerra Moreira, Jose Luciano ;

Pinheiro Gomes Bandeira, Tereza de Jesus ;

Costa Sidrim, Jose Julio .

JOURNAL OF MEDICAL MICROBIOLOGY, 2015, 64 :1277-1286

[3] In vitro anti-Candida activity of selective serotonin reuptake inhibitors against fluconazole-resistant strains and their activity against biofilm-forming isolates [J].

Costa Silva, Rose Anny ;

da Silva, Cecilia Rocha ;

de Andrade Neto, Joao Batista ;

da Silva, Anderson Ramos ;

Campos, Rosana Sousa ;

Sampaio, Leticia Serpa ;

Stefany Aires do Nascimento, Francisca Bruna ;

Gaspar, Brenda da Silva ;

da Cruz Fonseca, Said Goncalves ;

Alexandre Josino, Maria Aparecida ;

Grangeiro, Thalles Barbosa ;

Gaspar, Danielle Macedo ;

de Lucena, David Freitas ;

de Moraes, Manoel Odorico ;

Cavalcanti, Bruno Coelho ;

Nobre Junior, Helio Vitoriano .

MICROBIAL PATHOGENESIS, 2017, 107 :341-348

[4] Effect of the secretory leucocyte proteinase inhibitor (SLPI) on Candida albicans biological processes: A therapeutic alternative? [J].

da Rocha Curvelo, Jose Alexandre ;

Silva Barreto, Anna Lea ;

Portela, Maristela Barbosa ;

Alviano, Daniela Sales ;

Holandino, Carla ;

Souto-Padron, Thais ;

de Araujo Soares, Rosangela Maria .

ARCHIVES OF ORAL BIOLOGY, 2014, 59 (09) :928-937

[5]

de Andrade Neto Joao Batista, 2020, Future Microbiol, V15, P177, DOI 10.2217/fmb-2019-0082

[6] Molecular Docking and Structure-Based Drug Design Strategies [J].

Ferreira, Leonardo G. ;

dos Santos, Ricardo N. ;

Oliva, Glaucius ;

Andricopulo, Adriano D. .

MOLECULES, 2015, 20 (07) :13384-13421

[7]

Halgren TA, 1996, J COMPUT CHEM, V17, P490, DOI 10.1002/(SICI)1096-987X(199604)17:5/6<616::AID-JCC5>3.0.CO

[8]

2-X

[9] Avogadro: an advanced semantic chemical editor, visualization, and analysis platform [J].

Hanwell, Marcus D. ;

Curtis, Donald E. ;

Lonie, David C. ;

Vandermeersch, Tim ;

Zurek, Eva ;

Hutchison, Geoffrey R. .

JOURNAL OF CHEMINFORMATICS, 2012, 4

[10] Candida albicans Agglutinin-Like Sequence (AIs) Family Vignettes: A Review of AIs Protien Structure and Function [J].

Hoyer, Lois L. ;

Cota, Ernesto .

FRONTIERS IN MICROBIOLOGY, 2016, 7

← 1 2 3 4 →