Lysine enhances the effect of amphotericin B against <italic>Candida albicans in vitro</italic>

Abstract

Amphotericin B (AmB) is a polyene antibiotic produced by Streptomyces nodosus and has been used for >50 years in the treatment of acute systemic fungal infections. In the present study, we demonstrated that lysine, an essential amino acid, could enhance the effect of AmB against Candida albicans in vitro, although lysine itself did not exert a fungicidal effect. In addition, the combination of AmB with lysine could provide an enhanced action against Candida parapsilosis and Cryptococcus neoformans compared with AmB alone. Lysine could also enhance the antifungal effect of caspofungin or nystatin. An enhanced effect of the combination of lysine with AmB was observed for the prevention of biofilm and hypha formation. Furthermore, our results demonstrated that lysine-mediated oxidative damage, such as the generation of endogenous reactive oxygen species, may be the mechanism underlying the enhancing effect of lysine on AmB. Our results also showed that CaMCA1 gene plays an important role in increasing the sensitivity of C. albicans cells upon AmB treatment. Using AmB together with lysine may be a promising strategy for the therapy of disseminated candidiasis.

Liposoluble Chemical Constituents in Danshen

“…Furthermore, the following experiment showed that tanshinone IIA can remove lipid free radicals produced by Fe 3+ , which induces the lipid peroxidation of the mitochondria membrane. When a dose of 0.8 mg/ mg/Pr is given, the clearance rate is nearly 70 % [60]. From these two experiments, we can conclude that tanshinone IIA acts as a chain blocking agent to remove free radicals by inhibiting or breaking off oxidative chains rather than directly removing free radicals.…”

“…The compounds biogenetically related to 59 also include norsalvioxide (60) and miltipolone (61). After an oxygen atom is taken off the methenyl group of miltipolone, ring B is aromatized to obtain salviolone [35].…”

Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant Candida spp.

“…1 . 1 4.2.26 (1E,4Z,6E)-1,7-BisIJ3,4-dihydroxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one (24). A suspension of curcumin (368 mg, 1 mmol) in 20 mL of anhydrous dichloromethane was cooled to −20°C under a nitrogen atmosphere and 6.5 mL of 1 M boron tribromide solution in dichloromethane (6.5 equiv.)…”

“…4.3.2 Antifungal susceptibility assays (turbidity observation method). Antifungal susceptibility assays were done according to Zhao et al 24 with little modification. The initial concentration of the fluconazole-resistant C. tropicalis 087 suspension was 10 4 CFU ml −1 in RPMI 1640 medium in glass tubes.…”

Multimodal Role of Amino Acids in Microbial Control and Drug Development

“…Amino acids may have potential therapeutic applications as antibiofilm agents and drug excipients as the available literature mentions numerous research studies on the role of amino acids as potential antibiofilm agents and drug excipients. One such study found that the fungicidal and antibiofilm activity of antifungal drug amphotericin B was enhanced when combined (physically) with amino acid lysine, through a possible lysine-mediated generation of endogenous reactive oxygen species (ROS) [130]. The antibacterial and antibiofilm activity of known drugs such as clindamycin, cefazolin, oxacillin, rifampin, and vancomycin (for Gram-positive) and amikacin, colistin, ciprofloxacin, imipenem, and ceftazidime (for Gram-negative) has been reported to have enhanced when combined (physically) with d-amino acids [51].…”