Investigating the impact of posaconazole prophylaxis on systematic fungal screening using galactomannan antigen, Aspergillus fumigatus qPCR, and Mucorales qPCR

2021 ◽  
Vol 31 (2) ◽  
pp. 101117
Author(s):  
Anne-Pauline Bellanger ◽  
Natacha Tatoyan ◽  
Tess Monnot ◽  
Eric Deconinck ◽  
Emeline Scherer ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Galactomannan Antigen ◽  
The Impact

scholarly journals Preexposure to Isavuconazole Increases the Virulence of Mucorales but Not Aspergillus fumigatus in a Drosophila melanogaster Infection Model

2018 ◽  
Vol 63 (2) ◽  
pp. e01896-18 ◽  
Author(s):  
Sebastian Wurster ◽  
Russell E. Lewis ◽  
Nathaniel D. Albert ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Drosophila Melanogaster ◽  
Aspergillus Fumigatus ◽  
Clinical Isolates ◽  
Infection Model ◽  
Content Type ◽  
The Impact

ABSTRACT Breakthrough mucormycosis in patients receiving isavuconazole prophylaxis or therapy has been reported. We compared the impact of isavuconazole and voriconazole exposure on the virulence of clinical isolates of Aspergillus fumigatus and different Mucorales species in a Drosophila melanogaster infection model. In contrast to A. fumigatus, a hypervirulent phenotype was found in all tested Mucorales upon preexposure to either voriconazole or isavuconazole. These findings may contribute to the explanation of breakthrough mucormycosis in isavuconazole-treated patients.

Detection of Aspergillus fumigatus by Polymerase Chain Reaction (PCR)

2019 ◽  
Vol 10 (04) ◽  
pp. 655-661
Author(s):  
Zainab H Abood AL-Asadi
Keyword(s):  
Polymerase Chain Reaction ◽  
Aspergillus Fumigatus ◽  
Oligonucleotide Primer ◽  
Rrna Gene ◽  
Fungal Culture ◽  
Chain Reaction ◽  
Isolation And Identification ◽  
Internal Transcribed Spacer Region ◽  
Polymerase Chain ◽  
The Impact

Aspergillosis refers to fungi infections of the respiratory tract caused by Aspergillus species, especially Aspergillus fumigatus. Infection of A. fumigatus was increased in the last few years due to either resistances to antibiotics or the influence of other factors such as other fungal infections. The present study aimed to review the impact of Aspergillus fumigatus in Aspergillosis cases, and study the role of Singleplex PCR for amplification of ITS1, ITS4 of rRNA gene in the detection of fungal isolate. In this study, One hundred sputum samples were collected from patients admitted to the specialize chest and respiratory diseases center / Baghdad who were suffering from respiratory problems. During these studied, molds were isolation and identification based on Conventional method (Direct microscopy by using 10% KOH, and fungal culture was done on Sabouraud Dextrose agar supplemented with chloramphenicol and on Czapek-Dox agar incubated at 37°C and examined for 3-7 days then macroscopic, microscopic examination of the colony by(lactophenol cotton blue stain )and molecular methods by using Polymerase chain reaction (PCR)technique for identification. The 10% KOH examination was positive for 35 cases, while laboratory culturing was positive for 53 cases. Aspergillus sp were isolated from 44(83%) patients; A. fumigatus was isolated in 23 (42. 4%) patients while A. flavus, A. niger, and A. terreus were isolated from 11 (20. 08%), (13. 2%) and 3 (5. 7%) patients respectively, also isolated Penicillium spp. at percentage 1(1. 9%). In this study. The ages of participants ranged from 10-70years with a mean age of 34years, the males were more susceptible to fungal infection, were recorded 35/53 (66. 3), compared to females were 18/53 (33. 96). The infection of fungi was more prevalent in ages 30-40recorded 26(53. 06%) followed by ages 40-50, 13(26. 5), while the lowest infection recorded in the age group 10- 20 years was 2(2. 04%). DNA isolated from twenty-three A. fumigatus isolates was used as a template, and the specific of oligonucleotide primer sequences were used in conventional PCR to detect the presence of internal transcribed spacer region ( ITS) region of the rRNA gene for Aspergillus fumigates. The results of the PCR amplification of the rRNA gene showed that this gene was present in 19 samples out 23 positive samples which isolation with a PCR product size of approximated 385 bp, while 4 samples out 23 positive samples showed negative results for the presence of this gene as indicated by the absence of the PCR products in their relevant lanes. Statistical analysis revealed that the PCR to have a sensitivity of 95. 1% in the detection of Aspergillus fumigatus in Aspergillosis cases. Polymerase chain reaction (PCR) is a rapid, specific, and sensitive method to detect Aspergillus fumigatus in aspergillosis cases of humans.

scholarly journals Risk factors for respiratory Aspergillus fumigatus in German Cystic Fibrosis patients and impact on lung function

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Uta Düesberg ◽  
Julia Wosniok ◽  
Lutz Naehrlich ◽  
Patience Eschenhagen ◽  
Carsten Schwarz
Keyword(s):  
Risk Factors ◽  
Cystic Fibrosis ◽  
Lung Function ◽  
Aspergillus Fumigatus ◽  
Age Groups ◽  
Antibiotic Use ◽  
Lower Lung ◽  
Lung Infections ◽  
The Impact

Abstract Airway inflammation and chronic lung infections in cystic fibrosis (CF) patients are mostly caused by bacteria, e.g. Pseudomonas aeruginosa (PA). The role of fungi in the CF lung is still not well elucidated, but evidence for a harmful and complex role is getting stronger. The most common filamentous fungus in CF is Aspergillus fumigatus (AF). Age and continuous antibiotic treatment have been discussed as risk factors for AF colonisation but did not differentiate between transient and persistent AF colonisation. Also, the impact of co-colonisation of PA and AF on lung function is still under investigation. Data from patients with CF registered in the German Cystic Fibrosis Registry database in 2016 and 2017 were retrospectively analysed, involving descriptive and multivariate analysis to assess risk factors for transient or persistent AF colonisation. Age represented an independent risk factor for persistent AF colonisation. Prevalence was low in children less than ten years, highest in the middle age and getting lower in higher age (≥ 50 years). Continuous antibiotic lung treatment was significantly associated with AF prevalence in all age groups. CF patients with chronic PA infection had a lower lung function (FEV1%predicted), which was not influenced by an additional AF colonisation. AF colonisation without chronic PA infection, however, was significantly associated with a lower function, too. Older age up to 49 years and continuous antibiotic use were found to be the main risk factors for AF permanent colonisation. AF might be associated with decrease of lung function if not disguised by chronic PA infection.

scholarly journals Disruption of the Phospholipase D Gene Attenuates the Virulence of Aspergillus fumigatus

2011 ◽  
Vol 80 (1) ◽  
pp. 429-440 ◽  
Author(s):  
Xianping Li ◽  
Meihua Gao ◽  
Xuelin Han ◽  
Sha Tao ◽  
Dongyu Zheng ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Aspergillus Fumigatus ◽  
Phospholipase D ◽  
Morphological Characteristics ◽  
Pathogenic Fungi ◽  
Lung Epithelial Cells ◽  
Gene Encoding ◽  
Content Type ◽  
Important Virulence Factor ◽  
The Impact

ABSTRACTAspergillus fumigatusis the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases onA. fumigatusvirulence is rather limited. In this study, disruption of thepldgene encoding phospholipase D (PLD), an important member of the phospholipase protein family inA. fumigatus, was confirmed to significantly decrease both intracellular and extracellular PLD activity ofA. fumigatus. Thepldgene disruption did not alter conidial morphological characteristics, germination, growth, and biofilm formation but significantly suppressed the internalization ofA. fumigatusinto A549 epithelial cells without affecting conidial adhesion to epithelial cells. Importantly, the suppressed internalization was fully rescued in the presence of 100 μM phosphatidic acid, the PLD product. Indeed, complementation ofpldrestored the PLD activity and internalization capacity ofA. fumigatus. Phagocytosis ofA. fumigatusconidia by J774 macrophages was not affected by the absence of thepldgene. Pretreatment of conidia with 1-butanol and a specific PLD inhibitor decreased the internalization ofA. fumigatusinto A549 epithelial cells but had no effect on phagocytosis by J774 macrophages. Finally, loss of thepldgene attenuated the virulence ofA. fumigatusin mice immunosuppressed with hydrocortisone acetate but not with cyclophosphamide. These data suggest that PLD ofA. fumigatusregulates its internalization into lung epithelial cells and may represent an important virulence factor forA. fumigatusinfection.

scholarly journals Tracing patterns of evolution and acquisition of drug resistant Aspergillus fumigatus infection from the environment using population genomics

2021 ◽  
Author(s):  
Johanna Rhodes ◽  
Alireza Abdolrasouli ◽  
Katie Dunne ◽  
Thomas R. Sewell ◽  
Yuyi Zhang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Aspergillus Fumigatus ◽  
Population Genomics ◽  
Clinical Importance ◽  
Antifungal Drugs ◽  
Environmental Drivers ◽  
Drug Resistant ◽  
A Genome ◽  
Tract Infections ◽  
The Impact

Infections caused by opportunistic fungal pathogens are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about the extent to which susceptible patients acquire infection from drug resistant genotypes in the environment. Here, we present a population genomic analysis of the mould Aspergillus fumigatus from across the United Kingdom and Republic of Ireland. First, we show occurrences where azole resistant isolates of near identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Second, we find that the fungus is structured into two clades ('A' and 'B') with little interclade recombination and the majority of environmental azole resistance genetically clustered inside Clade A. Genome-scans show the impact of selective sweeps across multiple regions of the genome. These signatures of positive selection are seen in regions containing canonical genes encoding fungicide resistance in the ergosterol biosynthetic pathway, whilst other regions under selection have no defined function. Phenotyping identified genes in these regions that could act as modifiers of resistance showing the utility of reverse genetic approaches to dissect the complex genomic architecture of fungal drug resistance. Understanding the environmental drivers and genetic basis of evolving fungal drug resistance needs urgent attention, especially in light of increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.

Detection of Aspergillus fumigatus by Polymerase Chain Reaction(PCR)

2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Zainab H Abood AL-Asadi
Keyword(s):  
Polymerase Chain Reaction ◽  
Aspergillus Fumigatus ◽  
Oligonucleotide Primer ◽  
Rrna Gene ◽  
Fungal Culture ◽  
Chain Reaction ◽  
Isolation And Identification ◽  
Internal Transcribed Spacer Region ◽  
Polymerase Chain ◽  
The Impact

Aspergillosis refers to fungi infections of the respiratory tract caused by Aspergillus species especially Aspergillus fumigatus.Infection of A. fumigatus were increased in last few years , due to either resistances to antibiotics or to influence of other factors such as other fungal infections.The aims of the present study were to review the impact of Aspergillus fumigatus in Aspergillosis cases, and study the role of Singleplex PCR for amplification of ITS1,ITS4 of rRNA gene in the detection of fungal isolate . In this study One hundred sputum samples were collected from patients admitted to the specialize chest and respiratory diseases center / Baghdad who were suffering from respiratory problems. During these studied, molds were isolation and identification based on Conventional method (Direct microscopy by using 10% KOH, and fungal culture was done on Sabouraud Dextrose agar supplemented with chloramphenicol and on Czapek-Dox agar incubated at 37°C and examined for 3-7 days then macroscopic, microscopic examination of the colony by(lactophenol cotton blue stain )and molecular methods by using Polymerase chain reaction (PCR)technique foridentification. The 10% KOH examination was positive for 35 cases while laboratory culturing was positive for 53 cases. Aspergillus sp were isolated from 44(83%) patients; A. fumigatus was isolated in 23 (42.4%) patients while A. flavus, A. niger, and A. terreus were isolated from 11 (20.08%), (13.2%) and 3 (5.7%) patients respectively, also isolated Penicillium spp. at percentage 1(1.9%).. In this study.The ages of participants ranged from 10-70years with a mean age of 34years, the males were more susceptible for fungal infection were recorded 35/53 (66.3), compared to females were 18/53 (33.96).The infection of fungi were more prevalent in ages 30-40recorded 26(53.06%) followed by ages 40-50 ,13(26.5), while the lowest infection recorded in age group 10- 20 years was 2(2.04%). DNA isolated from twenty three A.fumigatus isolates was used as template and the specific of oligonucleotide primer sequences were used in conventional PCR to detect the presence of internal transcribed spacer region ( ITS) region of the rRNA gene for Aspergillus fumigates. The results of the PCR amplification of the rRNA gene showed that, this gene was present in 19 samples out 23 positive samples which isolation with a PCR product size of approximated 385 bp, while 4 samples out 23 positive samples showed negative results for the presence of this gene as indicated by the absence of the PCR products in their relevant lanes.Statistical analysis revealed that the PCR to have a sensitivity of 95.1 % in the detection of Aspergillus fumigatus in Aspergillosis cases.Polymerase chain reaction (PCR) is a rapid, specific and sensitive method to detect Aspergillus fumigatus in aspergillosis cases of human.

scholarly journals Dexamethasone Promotes Aspergillus fumigatus Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2

2021 ◽  
Vol 7 (2) ◽  
pp. 70
Author(s):  
Maureen K. Luvanda ◽  
Wilfried Posch ◽  
Jonathan Vosper ◽  
Viktoria Zaderer ◽  
Asma Noureen ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Immune Modulation ◽  
Fungal Infections ◽  
Macrophage Polarization ◽  
Corticosteroid Treatment ◽  
High Morbidity ◽  
Phenotypic Properties ◽  
Metabolic Switch ◽  
Anti Inflammatory ◽  
The Impact

Since long-term corticosteroid treatment is associated with emerging opportunistic fungal infections causing high morbidity and mortality in immune-suppressed individuals, here we characterized the impact of dexamethasone (Dex) treatment on Aspergillus fumigatus-related immune modulation. We found by high content screening and flow cytometric analyses that during monocyte-to-macrophage differentiation, as little as 0.1 µg/mL Dex resulted in a shift in macrophage polarization from M1 to M2-like macrophages. This macrophage repolarization mediated via Dex was characterized by significant upregulation of the M2 marker CD163 and downmodulation of M1 markers CD40 and CD86 as well as changes in phenotypic properties and adherence. These Dex-mediated phenotypic alterations were furthermore associated with a metabolic switch in macrophages orchestrated via PKM2. Such treated macrophages lost their ability to prevent Aspergillus fumigatus germination, which was correlated with accelerated fungal growth, destruction of macrophages, and induction of an anti-inflammatory cytokine profile. Taken together, repolarization of macrophages following corticosteroid treatment and concomitant switch to an anti-inflammatory phenotype might play a prominent role in triggering invasive aspergillosis (IA) due to suppression of innate immunological responses necessary to combat extensive fungal outgrowth.

scholarly journals Meiosis in the human pathogen Aspergillus fumigatus has the highest known number of crossovers

2022 ◽  
Author(s):  
Ben Auxier ◽  
Frank Becker ◽  
Reindert Nijland ◽  
Alfons J.M. Debets ◽  
Joost van den Heuvel ◽  
...  
Keyword(s):  
Population Genetics ◽  
Aspergillus Fumigatus ◽  
Sexual Reproduction ◽  
Recombination Rate ◽  
Sexual Cycle ◽  
Human Pathogen ◽  
Crossover Rate ◽  
Eukaryotic Species ◽  
Global Spread ◽  
The Impact

Evidence from both population genetics and a laboratory sexual cycle indicate that sex is common in the fungus Aspergillus fumigatus. However, the impact of sexual reproduction has remained unclear. Here, we show that meiosis in A. fumigatus involves the highest known recombination rate, producing ~29 crossovers per chromosome. This represents the highest known crossover rate for any Eukaryotic species. We validate this recombination rate by mapping resistance to acriflavine, a common genetic marker. We further show that this recombination rate can produce the commonly encountered TR34/L98H azole-resistant cyp51A haplotype in each sexual event, facilitating its rapid and global spread. Understanding the consequences of this unparalleled crossover rate will not only enrich our genetic understanding of this emergent human pathogen, but of meiosis in general.

scholarly journals Azole resistant Aspergillus fumigatus clinical isolate screening in azole-containing agar plates (EUCAST E.Def 10.1): low impact of plastic trays used and poor performance in cryptic species

2021 ◽  
Author(s):  
Julia Serrano-Lobo ◽  
Ana Gómez ◽  
Belén Rodríguez-Sánchez ◽  
Patricia Muñoz ◽  
Pilar Escribano ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Cryptic Species ◽  
Screening Method ◽  
Fungal Growth ◽  
Poor Performance ◽  
Sensu Stricto ◽  
Azole Resistance ◽  
Major Error ◽  
Agar Method ◽  
The Impact

Azole-containing agar is used in routine Aspergillus fumigatus azole resistance screening. We evaluated the impact of the type of plastic used to prepare in-house agar plates on the procedurés performance against A. fumigatus sensu stricto and cryptic species. A. fumigatus sensu stricto (n=91) and cryptic species (n=52) were classified as susceptible or resistant (EUCAST E.Def 9.3.2; clinical breakpoints v10). In-house azole-containing agar plates were prepared following EUCAST E.Def 10.1 on three types of multi-dish plates. We assessed the sensitivity, specificity, and agreement values of the agar plates to screen for azole resistance. Overall, sensitivity and specificity values of the agar screening method were 100% and 93.3%, respectively. The type of tray used did not affect these values. All isolates harbouring TR 34 -L98H substitutions were classified as resistant to itraconazole and voriconazole by the agar method; however, false susceptibility (very major error) to posaconazole was not uncommon and happened in isolates with posaconazole MICs of 0.25 mg/L. Isolates harbouring G54R and TR 46 -Y121F-T289A substitutions were correctly classified by the agar method as itraconazole/posaconazole resistant and voriconazole-resistant, respectively. False resistance (major error) occurred in isolates showing tiny fungal growth. Finally, agreements between both procedures against cryptic species were much lower. Azole-containing agar plates are a convenient and reliable tool to screen for resistance in A. fumigatus sensu stricto ; the type of plastic tray used minimally affects the method. On the contrary, the performance against cryptic species is rather poor.

scholarly journals Human Dendritic Cells following Aspergillus fumigatus Infection Express the CCR7 Receptor and a Differential Pattern of Interleukin-12 (IL-12), IL-23, and IL-27 Cytokines, Which Lead to a Th1 Response

2006 ◽  
Vol 74 (3) ◽  
pp. 1480-1489 ◽  
Author(s):  
Valérie Gafa ◽  
Roberto Lande ◽  
Maria Cristina Gagliardi ◽  
Martina Severa ◽  
Elena Giacomini ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Aspergillus Fumigatus ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Th1 Response ◽  
Ifn Γ ◽  
Human Dendritic Cells ◽  
The Impact

ABSTRACT Aspergillus fumigatus is the most prevalent airborne fungal pathogen and causes fatal invasive aspergillosis in immunocompromised patients. Given the essential role of dendritic cells (DC) in initiating and regulating immune responses, we investigated the impact of A. fumigatus conidial infection on human DC. A. fumigatus conidia were rapidly internalized and induced the release of tumor necrosis factor alpha within the first 8 h. After A. fumigatus infection, the majority of DC underwent full maturation, although CCR7 expression was observed only in DC that had internalized the conidia. Additionally, the analysis of regulatory cytokines showed that infected DC simultaneously produced interleukin-12p70 (IL-12p70) and significant amounts of IL-10. IL-10 neutralization was not able to further increase IL-12p70 production from infected DC. Whereas the central role of IL-12 in the generation of Th1 cells has long been appreciated, recently two other members of the IL-12 family, IL-23 and IL-27, were reported to play important roles in the regulation of gamma interferon (IFN-γ) production from naïve and memory T cells. A. fumigatus-infected DC were also able to express high levels of IL-23p19 and low levels of IL-27p28 at later stages of infection. According to this expression pattern, A. fumigatus-infected DC were able to prime IFN-γ production of naïve T cells. Thus, this study on the expression of the new IL-12 family members controlling the Th1 response sheds light on a novel aspect of the contribution of DC to anti-Aspergillus immunity.

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