Miltefosine inhibits Candida albicans and non-albicans Candida spp. biofilms and impairs the dispersion of infectious cells.
Candida spp. can adhere to and form biofilms over different surfaces, becoming less susceptible to antifungal treatment. Resistance of biofilms to antifungal agents is multifactorial and the extracellular matrix (ECM) appears to play an important role. Among the few available antifungals for treatment of candidaemia, only the lipid formulations of amphotericin B (AmB) and the echinocandins are effective against biofilms. Our group has previously demonstrated that miltefosine has an important effect against Candida albicans biofilms. Thus, the aim of this work was to expand the analyses of the in vitro antibiofilm activity of miltefosine to non-albicans Candida spp. Miltefosine had significant antifungal activity against planktonic cells and the development of biofilms of C. albicans, Candida parapsilosis, Candida tropicalis and Candida glabrata. The activity profile in biofilms was superior to fluconazole and was similar to that of AmB and caspofungin. Biofilm-derived cells with their ECM extracted became as susceptible to miltefosine as planktonic cells, confirming the importance of the ECM in the biofilm resistant behaviour. Miltefosine also inhibited biofilm dispersion of cells at the same concentration needed to inhibit planktonic cell growth. The data obtained in this work reinforce the potent inhibitory activity of miltefosine on biofilms of the four most pathogenic Candida spp. and encourage further studies for the utilisation of this drug and/or structural analogues on biofilm-related infections.
Laboratório de Biologia Celular de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho 373, 21941-902 Rio de Janeiro, RJ, Brazil. Electronic address: taissa.vila@utsa.edu.
Taissa
T
Vila
Laboratório de Quimioterapia Antifúngica, Departamento de Microbiologia, Universidade de São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo, SP, Brazil.
Kelly
K
Ishida
Laboratório de Tecnologia em Bioquímica e Microscopia (LTBM), Centro de Ciências Biológicas e da Saúde, Centro Universitário Estadual da Zona Oeste, Av. Manuel Caldeira de Alvarenga 1203, 23070-200 Rio de Janeiro, RJ, Brazil.
Sergio Henrique
SH
Seabra
Laboratório de Biologia Celular de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho 373, 21941-902 Rio de Janeiro, RJ, Brazil.
Sonia
S
Rozental
D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D050296:Microbial Viability / Q000187:drug effects; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000935:Antifungal Agents; D010767:Phosphorylcholine; C039128:miltefosine
Biofilms; Candida; Dispersion; Extracellular matrix; Miltefosine; Resistance