Publication: Tipificación y análisis genómico de la resistencia a azoles en "Aspergillus fumigatus"
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2019-05-21
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Universidad Complutense de Madrid
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Abstract
Aspergillus fumigatus es un hongo filamentoso saprófito que habita en numerosos nichos ecológicos y generalmente en el suelo enriquecido con material orgánico. Como forma de dispersión, libera un gran número de esporas al aire que son inhaladas constantemente por animales y personas. Los individuos inmunocompetentes son capaces de eliminarlas eficazmente, sin embargo, los individuos inmunocomprometidos, especialmente los pacientes onco-hematológicos y trasplantados, no son capaces de deshacerse de ellas, colonizando el tejido pulmonar y produciendo enfermedad invasiva que en muchos casos deriva en diseminación hematógena. A. fumigatus es el principal agente causal de un grupo de patologías conocidas generalmente como aspergilosis pero que engloban una gran diversidad de manifestaciones clínicas que varían en función del tipo de infección y del estado inmunitario del huésped. Dentro de todas ellas, la aspergilosis invasiva (AI) es la manifestación clínica más severa así como la más común. Como el diagnóstico precoz es difícil y el tratamiento complejo se puede entender que los antifúngicos se utilicen a la menor sospecha de infección. Así, el protocolo de tratamiento de la enfermedad base incluye la profilaxis con antifúngicos. Esta situación ha facilitado el desarrollo de resistencias secundarias a los fármacos más empleados, los azoles. Los compuestos azólicos más importantes son el voriconazol, el itraconazol, el posaconazol y recientemente, el isavuconazol que inhiben la C14 α-esterol de metilasa bloqueando la síntesis del ergosterol y afectando al crecimiento fúngico...
Aspergillus fumigatus is one of the most ubiquitous saprophytic fungi which grows efficiently under a variety of environmental conditions but mainly on soil organic debris. A. fumigatuss porulates abundantly releasing airborne conidia which humans and animals are constantly inhaling. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms. However, in immunocompromised hosts, especially in onco-hematological patients and solid organ transplant recipients, A. fumigatus produces a pulmonary colonization which leads to invasive aspergillosis (IA) and sometimes to dissemination in the most severely predisposed patients., A. fumigatus is the main etiologic agent responsible for several human and animal diseases generally called aspergillosis which comprise a variety of clinical manifestations. There are several factors that contribute to aspergillosis, such as strain virulence and underlying hostimmune status. The most important clinical manifestation due to its severity and frequency is IA. Since a prompt initiation of antifungal treatment is a key element in improving survival rates, it is justified that azoles, which are the first line drugs used for treating aspergillosis, have been used as prophylactic therapy when these diseases are suspected. Consequently, it is expected that their extended use has contributed to the emergence of secondary resistance due to the intense exposure to this class of compounds. Azole drugs inhibit the C14 α-sterol demethylase that catalyzes a key step in the ergosterol biosynthesis. This interaction leads to ergosterol depletion that alters the fungal membrane with consequent fungal growth impairment. The most important azole compounds for managing patients with aspergillosis are voriconazole, itraconazole, posaconazole and, recently, isavuconazole...
Aspergillus fumigatus is one of the most ubiquitous saprophytic fungi which grows efficiently under a variety of environmental conditions but mainly on soil organic debris. A. fumigatuss porulates abundantly releasing airborne conidia which humans and animals are constantly inhaling. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms. However, in immunocompromised hosts, especially in onco-hematological patients and solid organ transplant recipients, A. fumigatus produces a pulmonary colonization which leads to invasive aspergillosis (IA) and sometimes to dissemination in the most severely predisposed patients., A. fumigatus is the main etiologic agent responsible for several human and animal diseases generally called aspergillosis which comprise a variety of clinical manifestations. There are several factors that contribute to aspergillosis, such as strain virulence and underlying hostimmune status. The most important clinical manifestation due to its severity and frequency is IA. Since a prompt initiation of antifungal treatment is a key element in improving survival rates, it is justified that azoles, which are the first line drugs used for treating aspergillosis, have been used as prophylactic therapy when these diseases are suspected. Consequently, it is expected that their extended use has contributed to the emergence of secondary resistance due to the intense exposure to this class of compounds. Azole drugs inhibit the C14 α-sterol demethylase that catalyzes a key step in the ergosterol biosynthesis. This interaction leads to ergosterol depletion that alters the fungal membrane with consequent fungal growth impairment. The most important azole compounds for managing patients with aspergillosis are voriconazole, itraconazole, posaconazole and, recently, isavuconazole...
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Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Genética, Fisiología y Microbiología, leída el 28-11-2018