Effect of Usnic Acid on Candida orthopsilosis and C. parapsilosis

Abstract

The activity of usnic acid against Candida orthopsilosis and Candida parapsilosis on planktonic and biofilm conditions was investigated by using a broth microdilution and microplate methods. Potent in vitro activities against different Candida species were obtained. The metabolic activity of sessile cells of C. parapsilosis complex was reduced by 80% at four times the 80% inhibitory concentration. The in vitro studies support further efforts to determine whether usnic acid can be used clinically to cure patients with Candida infections.A mong the Candida strains reported to cause human diseases, more than 17 different species have been identified (9,19). Many of these species have been observed to occur in the hemodialysis setting and/or to exhibit innate or acquired resistance to one or more established antifungal agents (4,12,13,16,21). In addition, the use of molecular identification methods has resulted in the identification of new species within larger species complex such as Candida orthopsilosis and Candida metapsilosis within the Candida parapsilosis complex (23). In particular, the percentage of isolates of C. orthopsilosis has been much higher in the C. parapsilosis complex isolates in Latin America (12.7%) (11).The small number of drugs available for fungal treatment encourages the search for new chemotherapeutic agents. Usnic acid (2,6-diacetyl-1,2,3,9b-tetrahydro-7,9-dihydroxy-8,9b-dimethyldibenzofuran-1,3-dione), a secondary lichen metabolite, is known to possesses antimicrobial properties in addition to antiviral, antiprotozoal, antiproliferative, anti-inflammatory, and analgesic activity (10).With respect to antimicrobial properties, usnic acid has activity against a number of planktonic Gram-positive bacteria and also has the capacity to control biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa (8). Indeed, the mechanism of action expressed by usnic acid is still unknown. According to the same study (8), usnic acid could inhibit quorum sensing in P. aeruginosa biofilms.Usnic acid has been tested against some Candida species, but there is no published data concerning its activity against the newly described species within the C. parapsilosis complex. Thus, we tested usnic acid in both planktonic or biofilm modes of growth in C. orthopsilosis and C. parapsilosis.Six isolates of C. parapsilosis complex able to form biofilms were collected from a hemodialysis unit located in the state of São Paulo, Brazil, between March 2006 and March 2007 obtained from 110 samples of water that were selected for testing. The identification of C. parapsilosis and C. orthopsilosis was confirmed by molecular methods as described previously (23). The MIC for usnic acid of planktonic C. parapsilosis complex cultures was determined in RPMI 1640 buffered with morpholinepropanesulfonic acid (MOPS) (both from Sigma Chemical Co., St. Louis, MO) using a broth microdilution method adapted from the CLSI approved standard (M27-A3) (6). Briefly, the usnic acid (Sigma) was dissolved in 5% (vol/vol) in dimethyl ...

Antibacterial activity of lichen secondary metabolite usnic acid is primarily caused by inhibition of RNA and DNA synthesis

“…Its activity against Candida spp. was also recently reported (Pires et al, 2012). It was also demonstrated that usnic acid may control biofilm formation of S. aureus mainly by killing the attached cells.…”

Enantioselective activity of usnic acid: a comprehensive review and future perspectives

“…)-usnic acid at the concentration of 4 lg/mL caused significant biofilm inhibition: 71.08% for azole-resistant and 87.84% for azole-sensitive C. albicans strains (Peralta et al 2017). Pires et al (2012) examined the antibiofilm effect of (? )-usnic acid on two Candida strains, C. orthopsilosis and C. parapsilosis.…”

Usnic acid inhibits biofilm formation and virulent morphological traits of Candida albicans

“…Several studies report about the antibiofilm ability of usnic acid against a variety of pathogens (Pompilio et al 2013;Francolini et al 2004;Nithyanand et al 2015) and it is also shown to exhibit anti-candidal activity against different Candida sp. (Yilmaz et al 2004;Pires et al 2012). Since targeting hyphal development and biofilms is considered to be a more effective and tangible measure to alleviate Candidal pathogenesis (Gauwerky et al 2009) the present study shows that usnic acid suppresses the above mentioned key virulence factors which is considered important during the etiology of C. albicans.…”