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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Caffeic acid and licochalcone A interfere with the glyoxylate cycle of Trichophyton rubrum

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Michelotto Cantelli, Bruna Aline [1] ; Bitencourt, Tamires Aparecida [1] ; Komoto, Tatiana Takahasi [1] ; Beleboni, Rene Oliveira [1] ; Marins, Mozart [1] ; Fachin, Ana Lucia [1]
Total Authors: 6
[1] Univ Ribeirao Preto, Biotechnol Unit, Ribeirao Preto, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: BIOMEDICINE & PHARMACOTHERAPY; v. 96, p. 1389-1394, DEC 2017.
Web of Science Citations: 4

Trichophyton rubrum is the most common causative agent of dermatomycoses worldwide. Despite the increasing incidence of fungal infections, the number of commercially available antifungal drugs is limited, mainly because of the biochemical similarities between fungal and mammalian cells. Biomolecules of different origins might lead to the discovery of new pharmacological targets that are more specific to the fungal cell. In this respect, caffeic acid (CA) and licochalcone A (LicoA) exhibit activity against some human pathogenic fungi by acting on important fungal molecular targets. The glyoxylate cycle is involved in the adaptation of fungal cells inside the human cell and is well established for some fungi of clinical interest. Activation of this cycle is related to the survival of fungi in nutrient-limited environments. However, little is known about the involvement of the glyoxylate cycle in this process in dermatophytes. The objective of this study was to evaluate the antifungal activity of CA and LicoA against T. rubrum, investigating specifically the effect of these compounds on important antifungal targets such as ergosterol synthesis, cell wall and glyoxylate cycle. The minimum inhibitory concentration was 86.59 mu M for CA and 11.52 mu M for LicoA. Plasma membrane damage and a reduction in ergosterol levels were observed after the exposure of T. rubrum to CA, but not to LicoA. Evaluation of gene expression in T. rubrum co-cultured with human keratinocytes (HaCat) in the absence of the antifungal compounds showed induction of genes related to the ergosterol biosynthesis pathway and genes encoding enzymes involved in cell wall synthesis and in the glyoxylate cycle. The same genes were significantly repressed after exposure of the co-culture to subinhibitory concentrations of CA and LicoA. The enzymatic activity of isocitrate lyase was reduced in the presence of LicoA and a moderate reduction was observed in the presence of CA. These results indicate that CA and LicoA act on targets that play important roles in pathogen-host interactions, in antifungal activity and, especially, in the glyoxylate cycle. (AU)

FAPESP's process: 15/23435-8 - Molecular mechanisms involved in resistance and adaptive response to fungal inhibitors
Grantee:Tamires Aparecida Bitencourt
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 14/23841-3 - Study of natural compounds with antifungal activity to elucidate the action mechanism
Grantee:Ana Lucia Fachin Saltoratto
Support type: Regular Research Grants
FAPESP's process: 16/22701-9 - Study of the response to antifungal and fungal-host interaction of T.rubrum dermatophyte using different models of infection
Grantee:Ana Lucia Fachin Saltoratto
Support type: Regular Research Grants