Unraveling the secrets of Histoplasma capsulatum. A model to study morphogenic adaptation during parasite host/host interaction.
Early in the developmental period of microbiology, Pasteur first observed the phenomenon of dimorphism in fungi when he noticed that the bread mold Mucor grew as a filamentous mold aerobically on the surface of broth cultures but at the bottom of the flask where the environment was anaerobic it reproduced as budding yeast cells. Several infectious fungal pathogens of humans, namely Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenkii, and Coccidioides immitis change from a multicellular filamentous form to an unicellular morphology when they invade tissues. The ability of pathogenic fungi to assume a different shape is referred to as dimorphism. This phenomenon has intrigued clinicians, and medical mycologists since its discovery at the turn of the century. The ability of pathogens to initiate infection, invade host tissues and survive in mammalian hosts is critically linked to the induction of specific gene products. In dimorphic fungi, developmentally regulated gene expression is particularly important, since they may exist in phylogenetically distinct hosts with different body temperatures. Using Histoplasma capsulatum as a model to study parasite-host interactions at the biochemical and molecular level, my laboratory has attempted to relate the clinical spectrum of disease to natural variations in the characteristics of this organism and to adaptations it must make as a saprobe and a parasite. Histoplasma capsulatum is the etiologic agent of histoplasmosis, a respiratory infection that is world-wide in distribution. As a saprobe in soil it is mycelial, but it becomes a budding yeast as a parasite in susceptible hosts. These morphological phases can be reversibly reproduced in vitro by shifting the temperature from 25 degrees C, at which it is mycelial, to 37 degrees C, when it becomes a budding yeast. The process of mycelial-to-yeast conversion is of particular interest since it is triggered by an increase in temperature and conversion to virulence. Viable mycelial fragments and conidia become airborne and enter the pulmonary tract by inhalation after which the fungus rapidly disseminates to other organs. Progressive disseminated histoplasmosis along with candidiasis, cryptococcosis, and invasive aspergillosis are opportunistic fungal infections in patients who are immunosuppressed or otherwise debilitated. Importantly, they are diagnostic hallmarks of acquired immunodeficiency disease syndrome (AIDS). The clinical features of these infections and the genetic characteristics of the etiologic agents present unique parasite-host interactions that make them valuable research models to study. In the infected host, Histoplasma capsulatum encounters various environmental stresses to which it adapts by regulating the expression of specific genes.(ABSTRACT TRUNCATED AT 400 WORDS)
Maresca
B
B
International Institute of Genetics and Biophysics, Naples, Italy.
D000222:Adaptation, Physiological; D001483:Base Sequence; D044943:Fatty Acid Desaturases / Q000302:isolation & purification; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D006658:Histoplasma / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006660:Histoplasmosis / Q000382:microbiology; D006790:Host-Parasite Interactions; D006801:Humans; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013230:Stearoyl-CoA Desaturase
D006360:Heat-Shock Proteins; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C029627:delta-9 fatty acid desaturase