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Cadmium-dependent expression of a new metallothionein identified in Trichomonas vaginalis

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Abstract

Metallothioneins (MTs) have been identified in a wide variety of organisms from bacteria to humans. The biological functions of these MTs have a key role in metalloregulatory metabolism and its expression is induced in response to different stimuli, particularly by divalent metal cations. Also, the action of MTs have been implicated in the survival of pathogens in presence of microbicidal concentration of divalent cations, which allows the establishment of the infection. Trichomonas vaginalis is a protozoan parasite that adapts to the microenvironment of the male urogenital tract, where cations such as zinc (Zn2+) and cadmium (Cd2+) are present. Nevertheless, the molecular mechanisms of metal tolerance and homeostasis is not yet dilucidated in this parasite. In this study, we have identified 4 potential MT-like sequences (tvmt´s) in T. vaginalis genome. Because tvmt-2, -3, and -4 corresponds to truncated partial genes, we characterized the trichomonad tvmt-1 gene. The bioinformatic analyses and the predicted protein (TvMT-1) show similar properties to the reported in other MTs. The expression patterns of tvmt-1 in the presence of several divalent cations (Fe2+, Mn2+, Zn2+ and Cd2+) were analyzed and we demonstrated that Cd2+ induce significantly their expression. By indirect immunofluorescence assays, we corroborated this positive regulation of TvMT-1 in the cytoplasm of parasites grown in the presence of Cd2+. The tvmt-1 promoter contains putative metal responsive elements, which are probably the responsible for the Cd2+-dependent expression of this gene. Our results suggest that tvmt-1 gene encode a metallothionein that may be responsible for the homeostatis and detoxification of Cd+2 in T. vaginalis.

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Abbreviations

MT:

Metallothioneins

TvMT:

Metallothionein of Trichomonas vaginalis

Zn2+ :

Zinc

Cd2+ :

Cadmium

Cu2+ :

Copper

MTF-1:

Metal transcription factor

MRE:

Metal response element

Fe2+ :

Iron

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Acknowledgements

This work was supported by UACM and a grant from CONACyT (83808) Mexico (to M.E.A.S.). JAMR was supported by a scholarship from CONACYT (296788). We acknowledge Ph.D.Vadim Pérez Koldenkova for their technical assistance with confocal microscopy at Laboratorio Nacional de Microscopía Avanzada/Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social. We appreciate the technical assistance of Laura Vazquez Carrillo and Alfredo Padilla-Barberi.

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Authors and Affiliations

  1. Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México (UACM), San Lorenzo # 290, Col. Del Valle, CP 03100, Mexico City, Mexico

    Bryan Alexis Netzahualcoyotzi, Jonathan Puente-Rivera, Maximo Martínez Benitez, Jorge Antonio Moreno Reyes, Jose de Jesús Olivares Trejo & María Elizbeth Alvarez Sánchez

  2. Psychiatric Genetics Department, Clinical Research Branch, National Institute of Psychiatry, Ramón de la Fuente, Calzada México-Xochimilco 101, Colonia San Lorenzo Huipulco, Tlalpan, 14370, Mexico City, DF, Mexico

    Rodrigo Arreola

  3. Laboratorio de Bioquímica y Genética Molecular, Facultad de Química de la Universidad Autónoma de Yucatán, Mérida, 97069, Yucatán, Mexico

    Julio César Torres Romero

  4. Unidad de Investigacion Medica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatria, Centro Medico Nacional “Siglo XXI”, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico

    Rosalia Lira Carmona

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Correspondence to María Elizbeth Alvarez Sánchez.

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10534_2019_220_MOESM1_ESM.tif

Supplementary material 1 Fig. 1S Alignment of the MT1 and their homologues found in T. vaginalis. The proposed structural domains of the metal binding are repeated sequences. The N-terminal domains are different to others domains. Our predictions suggest that some domains (with 6-7 CYS) bind 2 divalent metals (Zn or Cd), other (with 9 CYS) 3 divalent metals and some (with 11 CYS) 4 divalent metal. Domains with 6-7 Cys can bind 2 metals, domains with 9 Cys can bind 3 metals and, domains with 11 Cys can bind 4 metals. The general consensus compared all repeated domains, the second consensus exclude the short domains (from XP_001321169.1: D5 and D7) and a Domain with modifications on the sequence from XP_001321197.1: D9). XP_001304130.1: TvMT-1 (TVAG_220940), XP_001584034.1: TvMT-2 (TVAG_182840), XP_001321169.1: TvMT-3 (TVAG_485930), XP_001321197.1: TvMT-4 (TVAG_486210) (TIFF 66979 kb)

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Netzahualcoyotzi, B.A., Puente-Rivera, J., Arreola, R. et al. Cadmium-dependent expression of a new metallothionein identified in Trichomonas vaginalis. Biometals 32, 887–899 (2019). https://doi.org/10.1007/s10534-019-00220-5

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