Molecular detection of Histoplasma capsulatum in the lung of a free-ranging common noctule (Nyctalus noctula) from France using the Hcp100 gene.

Histoplasma capsulatum is a dimorphic fungus that is widely distributed in the tropical or subtropical areas of the world and infects several mammalian hosts, mainly bats. Infective propagules grow in bat and bird droppings. A specific molecular marker, a highly sensitive fragment of a co-activator protein-coding gene (Hcp100), was used to detect H. capsulatum in lung samples of wild and captive bats from France using a nested polymerase chain reaction. To determine whether bats in France are potential carriers of H. capsulatum, 83 bats were sampled from two regions in France. Sixty-one specimens belonging to the Pteropus rodricensis (n = 45) and Rousettus aegyptiacus (n = 16) species were collected from a zoologic park (La Palmyre, western France). Twenty-two specimens were recovered from the Natural History Museum (Bourges) including the species Plecotus austriacus (n = 1), Pipistrellus pipistrellus (n = 3), and Nyctalus noctula (n = 18). From the lung DNA samples of 83 dead bats, only one sample of an N. noctula bat from Bourges amplified the H. capsulatum Hcp100 marker. The amplified product was sequenced and revealed a high similarity to the G217B H. capsulatum reference strain sequence that was deposited in the GenBank database. This finding suggests that H. capsulatum is an environmental pathogen in France that may infect bats.

Aspectos relevantes del marcador molecular Hcp100 de Histoplasma capsulatum y su potencial uso terapéutico en la histoplasmosis / Relevant aspects of the Hcp100 molecular marker of Histoplasma capsulatum and its potential therapeutic use in histoplasmosis

Antecedentes. Los hongos patógenos han desarrollado estrategias que involucran la expresión de genes que les ayudan a permanecer y multiplicarse en el huésped. La ausencia de las moléculas codificadas por estos genes podría interferir en el crecimiento y muerte de estos hongos. En el pasado, se reportó un gen (Hcp100) que codifica para una proteína coactivadora del hongo Histoplasma capsulatum, el cual se sobreexpresa después de 1h de contacto entre las levaduras del hongo y los macrófagos murinos. El producto de este gen, una proteína de 100kDa (Hcp100) de H. capsulatum, es probablemente una proteína regulatoria involucrada en los procesos necesarios de adaptación del hongo para la supervivencia en las condiciones hostiles intracelulares de los macrófagos. Un fragmento de 210pb del marcador Hcp100ha revelado ser una excelente herramienta para la detección molecular de H. capsulatum en muestras clínicas. El potencial uso de este gen como blanco terapéutico en Plasmodium falciparum ha sido explorado a través de la inhibición del gen y de la proteína p100 del parásito, logrando bloquear su crecimiento. Métodos. Tomando como base los antecedentes mencionados, la Hcp100 podría tener un papel clave en el desarrollo y mantenimiento de las levaduras de H. capsulatum dentro de los macrófagos. Resultados y conclusiones. Estudiar la probable función de la Hcp100 en la fase de levadura de este patógeno fúngico es relevante para entender su actividad y poder proponerla como un blanco terapéutico para el tratamiento de la histoplasmosis(AU)

Background. Fungal pathogens have developed strategies, involving genes expression that favors their persistence and multiplication in the host. The absence of molecules encoded by these genes could interfere with the growth and death of these fungi. In the past, a coactivator protein coding gene (Hcp100) of the fungus Histoplasma capsulatum was reported, which is overexpressed after 1h of contact between fungal yeast-cells and murine macrophages. The product of this gene, a protein of 100kDa (Hcp100) of H. capsulatum, is probably a regulatory protein involved in the processes required for fungal adaptation and its survival in the intracellular hostile conditions of the macrophages. A 210-bp fragment of the Hcp100 marker has proved to be an excellent tool for H. capsulatum molecular detection in clinical samples. The potential use of this gene as a therapeutic target in Plasmodium falciparum has been explored through the inhibition of both, the gene and the protein p100 of the parasite, by blocking its growth. Methods. Based on the above mentioned antecedents, we believe that the Hcp100 has an important role in the development and maintenance of the H. capsulatum yeast cells within macrophages. Results and conclusions. To study the probable function of Hcp100 in the yeast-phase of this fungal pathogen is relevant to understand its activity and to propose it as a therapeutic target for histoplasmosis treatment(AU)

[Relevant aspects of the Hcp100 molecular marker of Histoplasma capsulatum and its potential therapeutic use in histoplasmosis]. / Aspectos relevantes del marcador molecular Hcp100 de Histoplasma capsulatum y su potencial uso terapéutico en la histoplasmosis.

BACKGROUND: Fungal pathogens have developed strategies, involving genes expression that favors their persistence and multiplication in the host. The absence of molecules encoded by these genes could interfere with the growth and death of these fungi. In the past, a coactivator protein coding gene (Hcp100) of the fungus Histoplasma capsulatum was reported, which is overexpressed after 1h of contact between fungal yeast-cells and murine macrophages. The product of this gene, a protein of 100 kDa (Hcp100) of H. capsulatum, is probably a regulatory protein involved in the processes required for fungal adaptation and its survival in the intracellular hostile conditions of the macrophages. A 210-bp fragment of the Hcp100 marker has proved to be an excellent tool for H. capsulatum molecular detection in clinical samples. The potential use of this gene as a therapeutic target in Plasmodium falciparum has been explored through the inhibition of both, the gene and the protein p100 of the parasite, by blocking its growth. METHODS: Based on the above mentioned antecedents, we believe that the Hcp100 has an important role in the development and maintenance of the H. capsulatum yeast cells within macrophages. RESULTS AND CONCLUSIONS: To study the probable function of Hcp100 in the yeast-phase of this fungal pathogen is relevant to understand its activity and to propose it as a therapeutic target for histoplasmosis treatment.