In vitro synergistic effects of metergoline and antifungal agents against Candida krusei

Abstract

Metergoline, a serotonin receptor antagonist, was evaluated for its antifungal activity against the opportunistic human fungal pathogen Candida krusei by a broth microdilution assay. The minimal inhibitory concentration and minimal fungicidal concentration of metergoline against C. krusei were 4 and 8 μg ml(-1) respectively. Significant synergism was found in combination of metergoline with amphotericin B (fractional inhibitory concentration index: 0.375-0.5) by a chequerboard assay. Metergoline also inhibited extracellular phospholipase secretion in a dose-dependent manner, which may be a possible action mechanism of metergoline on C. krusei.

Metergoline-induced cell death in Candida krusei

“…For example, serotonin and its reuptake inhibitors have been shown to possess potent antifungal activity against Candida and Aspergillus species (LassFl€ orl et al 2001(LassFl€ orl et al , 2003Mayr et al 2005). In our previous study, we have demonstrated the antifungal activity of metergoline, a serotonin receptor antagonist, against FLC-resistant C. krusei isolates (MIC ¼ 4 mg ml À1 ) (Kang et al 2010b). To gain insight into the underlying antifungal mechanisms of metergoline in C. krusei, the present investigation was designed to examine the effects of metergoline on intracellular ROS level, mitochondrial homeostasis, and DNA fragmentation.…”

“…After 24 h of incubation at 35 C in a moist, dark incubator, fungal growth was measured spectrophotometrically at 595 nm. The MIC value was defined as the lowest concentration of the compound at which there was 80 % inhibition of visible growth, as indicated by the absorbance value, when compared with the solvent control (1 % DMSO) (Kang et al 2010b). …”

“…We have previously reported that metergoline, a serotonin receptor antagonist, exhibited considerable antifungal activity against C. krusei isolates and showed a synergistic effect with AMB (Kang et al 2010b). As a first step to understand its antifungal mechanism, its effect in triggering cell death responses was examined in the present investigation.…”

Promising antifungal activity of new oxadiazole against Candida krusei

“…Many studies have focused on synergistic effects as an alternative to the antifungal agents developed against Candida spp. [52][53][54][55][56][57]. However, there is a range of protocols with different interpretations [37,[58][59][60][61][62].…”

Synergistic and Antagonistic Drug Interactions in the Treatment of Systemic Fungal Infections

“…Of the 59 FLZ interacting molecules we identified, 10 have been previously described in various fungi, though 3 of those were reported as synergists while our testing revealed them to be antagonists (Ahmad et al, 2010;Butts et al, 2014;Cardoso et al, 2016;Eldesouky et al, 2018;Kang et al, 2010;Li et al, 2018;Marchetti et al, 2000;Quan et al, 2006;Robbins et al, 2015;Spitzer et al, 2011;Zhai et al, 2012). Additionally, we discovered synergistic molecules with a wide variety of bioactivities, suggesting that O2M identifies synergistic molecules with molecular mechanisms that can differ from that of the starting synergistic pair.…”