Population-Based Survey of Filamentous Fungi and Antifungal Resistance in Spain (FILPOP Study)

Alastruey‐Izquierdo, Ana; Mellado, Emilia; Peláez, Teresa; Pemán, Javier; Zapico, S.; Álvarez, M César; Rodríguez-Tudela, Juan Luis; Cuenca-Estrella, M.

doi:10.1128/aac.00383-13

Cited by 220 publications

(197 citation statements)

References 49 publications

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“…In addition, the antifungal profile of Aspergillus species complex frequently shows high MICs to multiple antifungals. 5,6 The goal of our study was to develop and validate in tissue samples a PCR based assay able to distinguish between A. fumigatus (azole susceptible) and A. lentulus (azole resistant) as well as to standardize an alternative mixed infection model in order to correlate in vitro susceptibility profiles with antifungal drug response.…”

Section: Discussionmentioning

confidence: 99%

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An alternative host model of a mixed fungal infection by azole susceptible and resistantAspergillusspp strains

Alcàzar-Fuoli¹,

Buitrago

Gómez-López

et al. 2015

Virulence

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Section: Discussionmentioning

confidence: 99%

“…3,4 The risk factors associated with these cryptic species are still undefined but it is known that they show remarkable high MICs to multiple antifungal agents. 5,6 The reasons for this change in fungal populations, as well as the emergence of drug resistance, are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

An alternative host model of a mixed fungal infection by azole susceptible and resistantAspergillusspp strains

Alcàzar-Fuoli¹,

Buitrago

Gómez-López

et al. 2015

Virulence

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“…This shift is mainly linked to the application of multilocus DNA sequence analysis in various studies, leading to the description of previously unknown "cryptic" Aspergillus species (5)(6)(7). In two population-based prospective studies in the United States and Spain, the prevalences of cryptic Aspergillus species detected in clinical specimens were found to be 10% and 12%, respectively (8,9). The molecular analysis of aspergilli collected from the Transplant-Associated Infection Surveillance Network (TRANSNET) from 24 transplant centers throughout the United States revealed that 10% of the isolates associated with invasive aspergillosis (IA) in transplant recipients were cryptic Aspergillus species (8).…”

mentioning

confidence: 99%

“…The molecular analysis of aspergilli collected from the Transplant-Associated Infection Surveillance Network (TRANSNET) from 24 transplant centers throughout the United States revealed that 10% of the isolates associated with invasive aspergillosis (IA) in transplant recipients were cryptic Aspergillus species (8). Similarly, the population-based FILPOP survey to investigate the epidemiology and antifungal resistance in Spanish clinical strains of filamentous fungi from deep-tissue samples, blood cultures, and respiratory samples reported that 12% of the isolates were cryptic Aspergillus species (9). The most notable findings in both studies were that the cryptic species had high in vitro MICs to multiple antifungal drugs, including azoles and amphotericin B (9,10).…”

mentioning

confidence: 99%

Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India

et al. 2016

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dAspergillus species cause a wide spectrum of clinical infections. Although Aspergillus fumigatus and Aspergillus flavus remain the most commonly isolated species in aspergillosis, in the last decade, rare and cryptic Aspergillus species have emerged in diverse clinical settings. The present study analyzed the distribution and in vitro antifungal susceptibility profiles of rare Aspergillus species in clinical samples from patients with suspected aspergillosis in 8 medical centers in India. Further, a matrix-assisted laser desorption ionization-time of flight mass spectrometry in-house database was developed to identify these clinically relevant Aspergillus species. ␤-Tubulin and calmodulin gene sequencing identified 45 rare Aspergillus isolates to the species level, except for a solitary isolate. They included 23 less common Aspergillus species belonging to 12 sections, mainly in Circumdati, Nidulantes, Flavi, Terrei, Versicolores, Aspergillus, and Nigri. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identified only 8 (38%) of the 23 rare Aspergillus isolates to the species level. Following the creation of an in-house database with the remaining 14 species not available in the Bruker database, the MALDI-TOF MS identification rate increased to 95%. Overall, high MICs of >2 g/ml were noted for amphotericin B in 29% of the rare Aspergillus species, followed by voriconazole in 20% and isavuconazole in 7%, whereas MICs of >0.5 g/ml for posaconazole were observed in 15% of the isolates. Regarding the clinical diagnoses in 45 patients with positive rare Aspergillus species cultures, 19 (42%) were regarded to represent colonization. In the remaining 26 patients, rare Aspergillus species were the etiologic agent of invasive, chronic, and allergic bronchopulmonary aspergillosis, allergic fungal rhinosinusitis, keratitis, and mycetoma.A spergillus species cause a wide spectrum of clinical infections, ranging from allergic to chronic and life-threatening invasive diseases (1). The most common pathogenic species implicated in aspergillosis are A. fumigatus, A. flavus, A. terreus, and rarely, A. niger. However, in the last decade, several reports have pointed to a shift in the etiology of aspergillosis and highlighted the emergence of cryptic and rare Aspergillus species in various clinical settings in both immunocompromised and immunocompetent hosts (2-4). This shift is mainly linked to the application of multilocus DNA sequence analysis in various studies, leading to the description of previously unknown "cryptic" Aspergillus species (5-7). In two population-based prospective studies in the United States and Spain, the prevalences of cryptic Aspergillus species detected in clinical specimens were found to be 10% and 12%, respectively (8, 9). The molecular analysis of aspergilli collected from the Transplant-Associated Infection Surveillance Network (TRANSNET) from 24 transplant centers throughout the United States revealed that 10% of the isolates associated with invasive aspe...

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“…However, it has also become the most serious etiological agent of invasive mold infections [2,3]. The small size of its conidia not only allows it to spread through the air [4], but also allows them to reach deep into the human respiratory system [5].…”

Section: Introductionmentioning

confidence: 99%

A possible role for fumagillin in cellular damage during host infection by Aspergillus fumigatus

et al. 2018

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Virulence mechanisms of the pathogenic fungus Aspergillus fumigatus are multifactorial and depend on the immune state of the host, but little is known about the fungal mechanism that develops during the process of lung invasion. In this study, microarray technology was combined with a histopathology evaluation of infected lungs so that the invasion strategy followed by the fungus could be described. To achieve this, an intranasal mice infection was performed to extract daily fungal samples from the infected lungs over four days post-infection. The pathological study revealed a heavy fungal progression throughout the lung, reaching the blood vessels on the third day after exposure and causing tissue necrosis. One percent of the fungal genome followed a differential expression pattern during this process. Strikingly, most of the genes of the intertwined fumagillin/pseurotin biosynthetic gene cluster were upregulated as were genes encoding lytic enzymes such as lipases, proteases (DppIV, DppV, Asp f 1 or Asp f 5) and chitinase (chiB1) as well as three genes related with pyomelanin biosynthesis process. Furthermore, we demonstrate that fumagillin is produced in an in vitro pneumocyte cell line infection model and that loss of fumagillin synthesis reduces epithelial cell damage. These results suggest that fumagillin contributes to tissue damage during invasive aspergillosis. Therefore, it is probable that A. fumigatus progresses through the lungs via the production of the mycotoxin fumagillin combined with the secretion of lytic enzymes that allow fungal growth, angioinvasion and the disruption of the lung parenchymal structure.

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Population-Based Survey of Filamentous Fungi and Antifungal Resistance in Spain (FILPOP Study)

Cited by 220 publications

References 49 publications

An alternative host model of a mixed fungal infection by azole susceptible and resistantAspergillusspp strains

An alternative host model of a mixed fungal infection by azole susceptible and resistantAspergillusspp strains

Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India

A possible role for fumagillin in cellular damage during host infection by Aspergillus fumigatus

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