N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine, a zinc chelator, inhibits biofilm and hyphal formation in Trichosporon asahii

Abstract

Objective: Trichosporon asahii is the major causative fungus of disseminated or deep-seated trichosporonosis and forms a biofilm on medical devices. Biofilm formation leads to antifungal drug resistance, so biofilm-related infections are relatively difficult to treat and infected devices often require surgical removal. Therefore, prevention of biofilm formation is important in clinical settings. In this study, to identify metal cations that affect biofilm formation, we evaluated the effects of cation chelators on biofilm formation in T. asahii. Results: We evaluated the effect of cation chelators on biofilm formation, since microorganisms must assimilate essential nutrients from their hosts to form and maintain biofilms. The inhibition by N,N,N′,N′-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) was greater than those by other cation chelators, such as deferoxamine, triethylenetetramine, and ethylenediaminetetraacetic acid. The inhibitory effect of TPEN was suppressed by the addition of zinc. TPEN also inhibited T. asahii hyphal formation, which is related to biofilm formation, and the inhibition was suppressed by the addition of zinc. These results suggest that zinc is essential for biofilm formation and hyphal formation. Thus, zinc chelators have the potential to be developed into a new treatment for biofilm-related infection caused by T. asahii.

Hyphal Growth in Trichosporon asahii Is Accelerated by the Addition of Magnesium

“…In fungi, zinc-binding transcription factors regulate filament formation ( 20 , 21 ). In T. asahii , the chelation of zinc by N , N , N′ , N′ -tetrakis (2-pyridylmethyl) ethylenediamine inhibits biofilm and hyphal formation ( 22 ). In contrast, C. albicans hyphal formation is enhanced by the addition of Mg 2+ rather than Zn 2+ ( 23 ).…”

Selective Metal Chelation by a Thiosemicarbazone Derivative Interferes with Mitochondrial Respiration and Ribosome Biogenesis in Candida albicans

“…For example, disruption of zinc transporter Zrt1 in C. albicans results in growth defects in zinc-restricted medium ( 17 ). A variety of zinc chelators have been demonstrated to exhibit antifungal activities or potentiate the efficacy of present antifungal drugs ( 18 – 21 ).…”

Tacrolimus inhibits stress responses and hyphal formation via the calcineurin signaling pathway in Trichosporon asahii

“…3 Hyphae and arthroconidia are observed in lesion tissue on histopathological examination 4 and play an important role in biofilm formation in T. asahii. 5,6 T. asahii needs to adapt to the host environment during infection. Therefore, inhibiting a crucial factor that regulates stress responses and hyphal formation in T. asahii could prevent infections.…”

“…T. asahii can change its morphology from yeast to hyphae and arthroconidia 3 . Hyphae and arthroconidia are observed in lesion tissue on histopathological examination 4 and play an important role in biofilm formation in T. asahii 5,6 . T. asahii needs to adapt to the host environment during infection.…”