Different colonization patterns of Aspergillus terreus in patients with cystic fibrosis

Due to the abnormal viscosity of airway secretions, patients with cystic fibrosis (CF) are athigh risk of fungal colonization of the respiratory tract. Aspergillus fumigatus is by far the most common fungal specie encountered in the CF context, but other species are increasingly reported such as Scedosporium spp. or Geosmithia argillacea, as well as other aspergilli including Aspergillus terreus. In our experience, this saprophytic fungus ranks the third among the filamentous fungi colonizing the respiratory tract of CF patients. Additionally, although relatively uncommon, infections caused by A. terreus present a high mortality rate due to its usually low susceptibility to systemic antifungals. Nevertheless, little is known about the epidemiology of A. terreus colonization/infections. In the present study, nine short tandem repeats of A. terreus were used to genotype 122 clinical isolates recovered from sputum samples from five patients with CF followed-up in two distinct hospitals in France (Angers and Giens hospitals). Sputum samples were collected over a two-month to seven-year period depending on the patients, and for each sample, all the obtained isolates were studied, with a maximum of five per sample. Three colonization patterns were observed. The first colonization pattern consisted of a chronic colonization (defined as the presence of the same genotype in at least two successive samples collected over a minimum period of two months) by a largely dominant genotype associated with two or three other genotypes found occasionally (patient 4) or over a short period (patient 3). The second colonization pattern consisted of a chronic colonization by two distinct genotypes simultaneously detected (patients 1 and 2). For the last patient (patient 5), who was followed during four years, 16 isolates recovered from 6 sputum samples were analyzed, corresponding to 8 genetically distinct genotypes which succeeded to each other. Numerous questions therefore raise from these different colonization patterns, regarding (i) the origin of the contamination of the patients by this relatively uncommon environmental fungus, (ii) the differences between genotypes in their ability to chronically colonize the airways of the CF patients, or (iii) the differences between CF patients in their individual susceptibility to same genotypes

Distribution of the different species of the Pseudallescheria boydii/Scedosporium apiospermum complex in French patients with cystic fibrosis

As various new sibling species within the Pseudallescheria boydii/Scedosporium apiospermum complex have been described recently with differences in their susceptibility to antifungals, this study was conducted in order to determine their respective frequency in cystic fibrosis. Results indicated that P. boydii largely predominated (62%), followed by S. apiospermum (24%), Scedosporium aurantiacum (10%) and Pseudallescheria minutispora (4%). Scedosporium dehoogii was not recovered in this study. The multiple correspondence factor analysis highlighted geographical discrepancies within species distribution: P. boydii was rarely encountered in Northern France, while S. apiospermum was less represented in the west of the country. Additionally, we demonstrated that all species encountered in the cystic fibrosis context were capable to chronically colonize the respiratory tract of patients. Molecular typing of a large set of environmental and clinical isolates should be conducted to delineate the epidemiology of each sibling species in the complex

Different colonization patterns of Aspergillus terreus in patients with cystic fibrosis

Patients with cystic fibrosis (CF) are at high risk of colonization of the respiratory tract by filamentous fungi, mainly Aspergillus fumigatus, but also other Aspergillus species including A. terreus. In our experience, this last fungus ranks the third among the filamentous fungi colonizing the respiratory tract of CF patients. Additionally, although uncommon, infections caused by A. terreus present a high mortality rate due to its usually low susceptibility to systemic antifungals. The recent development of a microsatellite typing system allowed us to investigate the molecular epidemiology of the airway colonization by this fungus in CF. Nine short tandem repeats of A. terreus were used to genotype multiple and sequential isolates from sputum samples from CF patients followed-up in Angers and Giens hospitals (France). Sputum samples were collected over a 2 month to 7 year period, and for each sample, all the obtained isolates were studied, with a maximum of five per sample. Thus a total of 122 isolates was studied, corresponding to 47 samples collected from 5 distinct patients. Three colonization patterns were observed. The first one consisted of a chronic colonization (presence of the same genotype in at least two successive samples collected over a minimum period of two months) by a largely dominant genotype associated with two or three other genotypes found occasionally (patient 1) or over a short period (patient 2). The second pattern consisted of a chronic colonization by two distinct genotypes simultaneously detected (patients 3 and 4). For the last patient (patient 5), 16 isolates recovered from 6 sputum samples collected during four years were analyzed, corresponding to 8 distinct genotypes which succeeded to each other. Numerous questions rise from these different colonization patterns, relatively uncommon environmental fungus; and (ii) differences between genotypes in their ability to chronically colonize the airways of the CF patients or differences between CF patients in their individual susceptibility to same genotypes. Strikingly, some genotypes shared by some patients were responsible for a chronic colonization in some patients while they rapidly disappear in other patients. A multicenter study should be conducted combining genetic study of the host and genotyping of fungal isolates, searching for predisposing factors to the airway colonization by A. terreus

Fungal detection in the real world?

International audienc

Weird moulds: pathogenic or innocent bystanders?

Cystic fibrosis is the most common genetic inherited disease in the European Caucasian population. It is due to mutations in the gene CFTR (for Cystic Fibrosis transmembrane conductance regulator) which encodes a chloride channel involved in electrolytic exchanges through the plasma membrane of numerous epithelial cell types. Several organs, therefore, are involved, but prognosis essentially depends on the severity of the lesions of the lungs. In the respiratory tract, mutations in the gene CFTR lead to a defect in the mucociliairy clearance and a thickening of the bronchial mucus, thus enabling the entrapment of the inhaled bacteria and fungal spores and  the  subsequent  colonization  of  the  airways  by  these microorganisms. Besides bacteria which are by far the most common cause of respiratory infections in this clinical context, several mold species may also colonize the respiratory tract of the patients. Although the clinical significance of their isolation from respiratory secretions has raised much controversy, the prevalence of fungal colonization of the airways is regularly increasing along with the increase in life expectancy. Moreover, this fungal colonization of the airways may also lead to true respiratory infections, including allergic broncho-pulmonary mycosis and pneumonia. Finally, due to their propensity to disseminate in an immunocompromised host and to their low susceptibilty or innate resistance to current antifungal drugs, one should be cautious if a lung transplantation is required, particularly in case of chronic colonization of the airways. Appropriate treatment, therefore, should be initiated as early as possible, which implies improved detection, identification and typing methods. Additionally, beside moulds, the respiratory tract of patients with CF often is colonized by yeasts, and a large variety of yeast species has been described in the CF context, Candida albicans, Candida glabrata and Candida parapsilosis being the most prevalent. Long considered completely devoid of clinical relevance, recent works on the airway colonization by Candida albicans as well as some clinical reports about the newly described Trichosporon mycotoxinivoranshave revived discussion about the pathogenic role of yeasts

Scedosporium species in cystic fibrosis

International audienc

Update on laboratory diagnosis of Aspergillus infection

International audienc

Ecology of Scedosporium Species: Present Knowledge and Future Research

The genus Scedosporium, which comprises at least five clinically relevant species, i.e. Scedosporium apiospermum, Scedosporium boydii, Scedosporium aurantiacum, Scedosporium dehoogii and Scedosporium minutisporum, ranks the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). This colonization of the airways is thought to contribute to the inflammatory reaction leading to a progressive deterioration of the lung function. Additionally, these colonizing fungi may lead to severe disseminated infections in case of lung transplantation. Therefore, considering the low susceptibility of Scedosporium species to all current antifungal drugs, preventive measures should be defined to reduce the risk of exposure to these fungi for non-colonized CF patients. With this in mind, several studies have been conducted to elucidate the ecology of these fungi and to define possible sources of patient contamination. This review will summarize the major outcomes of those studies, including: the clear demonstration that ecological niches of Scedosporium species are strongly impacted by human activities, and the ability of Scedosporium species to degrade aliphatic and aromatic pollutants which supports the high occurrence of these species in contaminated soils and polluted waters and makes them promising candidates for bioremediation purposes. Finally, prospects for future research in this field are proposed

Environnement et risque fongique au cours de la mucoviscidose

National audienc