Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Aspergillus fumigatus and Related Species Janyce A. Sugui1, Kyung J. Kwon-Chung1, Praveen Juvvadi2, Jean-Paul Latge´ 3, and William J. Steinbach2,4 1Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 2Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University, Durham, North Carolina 27715 3Unite´ des Aspergillus, Institut Pasteur, Paris 75724, France 4Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27710 Correspondence: [email protected] The genus Aspergillus contains etiologic agents of aspergillosis. The clinical manifestations of the disease range from allergic reaction to invasive pulmonary infection. Among the pathogenic aspergilli, Aspergillus fumigatus is most ubiquitous in the environment and is the major cause of the disease, followed by Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus nidulans, and several species in the section Fumigati that morphologi- cally resemble A. fumigatus. Patients that are at risk for acquiring aspergillosis are those with an altered immune system. Early diagnosis, species identification, and adequate antifungal therapy are key elements for treatment of the disease, especially in cases of pulmonary invasive aspergillosis that often advance very rapidly. Incorporating knowledge of the basic biology of Aspergillus species to that of the diseases that they cause is fundamental for further progress in the field. nvasive aspergillosis (IA) is one of the most lus to the fungus. More than 100 years later, Iserious clinical invasive fungal infections, re- Aspergillus fumigatus, the most important path- sulting in a high case-fatality rate among im- ogenic species of the genus, was described by www.perspectivesinmedicine.org munocompromised patients (Lin et al. 2001). Fresenius (1863), and the role of aspergilli in The disease is caused by saprophytic molds in human disease was first recognized by Virchow the genus Aspergillus. Established by Micheli in in 1856 (Virchow 1856). Virchow noticed the 1729, the genus Aspergillus was created to ac- similarity between the aspergilli described from commodate an asexual fungus that produces cases of animal infections and those he had spore chains or columns radiating from central observed in human disease. IA was later first structures. As a priest, Micheli recognized the recognized by Rankin, when he reported dis- resemblance of the spore-forming structures seminated aspergillosis in a patient with aplas- with that of the aspergillum (holy water sprin- tic anemia (Rankin 1953). For the subsequent kler), and therefore applied the name Aspergil- 60 years, the number of cases of IA increased Editors: Arturo Casadevall, Aaron P. Mitchell, Judith Berman, Kyung J. Kwon-Chung, John R. Perfect, and Joseph Heitman Additional Perspectives on Human Fungal Pathogens available at www.perspectivesinmedicine.org Copyright # 2014 Cold Spring Harbor Laboratory Press; all rights reserved Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a019786 1 Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press J.A. Sugui et al. substantially because of an increase in the num- in patients with chronic granulomatous disease ber of immunocompromised patients, such (CGD) (Cohen et al. 1981; Henriet et al. 2013). as those with malignancies, AIDS, solid organ A. fumigatus, A. flavus, and A. nidulans repro- transplantation (SOT), and those patients re- duce asexually and sexually, and their sexual ceiving immunosuppressive treatments for states have been described in the genus Neosar- countless underlying conditions (Denning 1998; torya (O’Gorman et al. 2009), Petromyces (Horn Kontoyiannis and Bodey 2002; Marr et al. et al. 2009), and Emericella (Kwon-Chung and 2002a). Bennett 1992), respectively. Because the de- scription of a sexual state merely completes the characterization of the fungus that is usually al- MYCOLOGY ready known (Kwon-Chung and Bennett 1992), these names have been abandoned in 2013 as the Taxonomy and Nomenclature of the fungal nomenclatural rule was changed to use Pathogenic Aspergillus Species only one name for one fungal species (Hawks- The genus Aspergillus is characterized by the worth et al. 2011). Sexual reproduction in het- formation of flask-shaped or cylindrical phi- erothallic aspergilli, such as A. fumigatus and alides either in a single or double series on the A. flavus, requires two strains of compatible surface of a vesicle at the apex of a conidiophore opposite mating types. Sexual reproduction in (Raper and Fennell 1965). Conidia are decidu- homothallic species, such as A. nidulans,is ous and globose, oblong to elliptical in shape, accomplished by a single strain harboring the and present various colors. In 1926, Thom and two compatible mating-type loci required for Church assembled all available information on mating. In heterothallic or homothallic species, Aspergillus in a monograph (Thom and Church mating produces ascospores, sexual spores 1926). In 1965, Raper and Fennell expanded this formed by meiosis, which are enclosed inside work by adding many new species and provided sexual fruiting bodies called cleistothecia. descriptions of the species classified into 18 Most ascospores have a furrow or slit (Hou- informal groups (Raper and Fennell 1965). In braken and Samson 2011). 1985, Gams and coinvestigators revised the groups and assigned them to 18 sections as a A. fumigatus and Other Pathogenic Members formal taxonomic status (Gams et al. 1985). of Section Fumigati Currently, there are approximately 250 species assigned to 17 sections in the family Aspergilla- The section Fumigati is of special interest to the ceae (Houbraken and Samson 2011) and this field of infectious diseases because this section www.perspectivesinmedicine.org number will continue to grow as new species includes not only A. fumigatus but also 11 other are described. The major species known to cause species as the etiologic agents of IA. Section disease in humans are found in five Aspergillus Fumigati is characterized by the formation of a sections: Fumigati, Flavi, Nigri, Terrei, and Ni- conidiophore with columnar conidial heads dulante. The most common species causing consisting of flask-shaped vesicles, uniseriate invasive disease is A. fumigatus in the section phialides, and long chains of conidia. Conidia Fumigati. Aspergillus flavus (section Flavi), As- are bluish-green to pale green, generally hydro- pergillus niger (section Nigri), and Aspergillus phobic, and have a size of 2.5–3.5 mm. It has terreus (section Ter rei) are secondary to A. fumi- been estimated that A. fumigatus is the etiologic gatus as etiologic agents in SOTand hematopoi- agent of various forms of aspergillosis in more etic stem cell transplantation (HSCT) recipients than 200,000 patients a year (Brown et al. 2012). as well as patients with leukemia (Perfect et al. It is unclear whether this estimate represents 2001; Marr et al. 2002a; Pagano et al. 2010; Pap- only those caused by A. fumigatus or includes pas et al. 2010). Aspergillus nidulans (section its morphologically indistinguishable sister spe- Nidulante) rarely causes IA in immunocompro- cies. Molecular diagnostic approaches have re- mised patients, but is a common etiology of IA vealed that there are at least 11 species that could 2 Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a019786 Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Aspergillus fumigatus and Related Species easily be confused with A. fumigatus based on (Latge´ 1999). A. fumigatus is more ubiquitous their conidial morphology. Besides A. fumiga- than other aspergilli owing to their superior tus, the sister species Aspergillus udagawae (Neo- ability to survive and grow in a wider range of sartorya udagawae), Aspergillus pseudofischeri environmental conditions compared to other (Neosartorya pseudofischeri), Aspergillus lentu- species. In the saprophytic cycle, conidia re- lus, Aspergillus felis, Aspergillus hiratsukae (Neo- leased from conidiophores are readily dispersed sartorya hiratsukae), Aspergillus fischeranus in the environment. Conidia remain dormant (Neosartorya fischeri), Aspergillus viridinutans, until encountering the environmental condi- Aspergillus fumisynnematus, Aspergillus fumiga- tions that allow activation of their metabolism. tiaffinis, Aspergillus novofumigatus, and Asper- Once metabolically active, conidia swell and gillus laciniosa (Neosartorya laciniosa)have germinate into hyphal filaments that grow been reported sporadically in cases of aspergil- into mycelium and produce conidia bearing losis. Of these, A. udagawae, A. lentulus, and fruiting structures (conidiophores) (Fig. 1). A. pseudofischeri have been reported more fre- Although A. fumigatus grows optimally at quently (Padhye et al. 1994; Alcazar-Fuoli et al. 37˚C, it can be isolated wherever soil and de- 2008; Alhambra et al. 2008; Vinh et al. 2009b; caying vegetation reach temperatures ranging Gyotoku et al. 2012; Zbinden et al. 2012) than between 12˚C and 65˚C, as well as pH between the other eight species (Lonial et al. 1997;