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Journal of Clinical Microbiology May 2024Azole resistance screening in can be routinely carried out by using azole-containing agar plates (E.Def 10.2 procedure); however, conidial suspension filtering and...
Azole resistance screening in using the azole-containing agar method (EUCAST E.Def 10.2): conidial suspension filtration and inoculum adjustment before inoculum preparation may not be needed.
UNLABELLED
Azole resistance screening in can be routinely carried out by using azole-containing agar plates (E.Def 10.2 procedure); however, conidial suspension filtering and inoculum adjustment before inoculum preparation are time-consuming. We evaluated whether skipping the filtration and inoculum adjustment steps negatively influenced the performance of the E.Def 10.2 procedure. isolates ( = 98), previously classified as azole susceptible or azole resistant (E.Def 9.4 method), were studied. Azole-resistant isolates had either the wild-type gene sequence ( = 1) or the following gene substitutions: TR-L98H ( = 41), G54R ( = 5), TR-Y121F-T289A ( = 1), or G448S ( = 1). In-house azole-containing agar plates were prepared according to the EUCAST E.Def 10.2 procedure. Conidial suspensions obtained by adding distilled water (Tween 20 0.1%) were either filtered and the inocula adjusted to 0.5 McFarland or left unfiltered and unadjusted. Agreements between the agar screening methods using inocula prepared by each procedure were high for itraconazole (99%), voriconazole (100%), and posaconazole (94.9%). Sensitivity and specificity (considering the susceptibility category as per the microdilution E.Def 9.4 method as the gold standard) of E.Def 10.2 were 100% to rule in or rule out resistance when unfiltered and unadjusted suspensions were used; the resistance phenotype of isolates harboring the TR-L98H, G54R, or TR-Y121F-T289A substitutions was correctly detected. Unfiltered and unadjusted conidial suspensions do not negatively influence the performance of the E.Def 10.2 method when screening for azole resistance in .
IMPORTANCE
Azole resistance screening in can be routinely carried out by using azole-containing plates (E.Def 10.2 procedure); however, conidial suspension filtering and inoculum adjustment before inoculation of plates are time-consuming. We, here, showed that unfiltered and unadjusted conidial suspensions do not negatively influence the performance of the E.Def 10.2 method when screening for azole resistance in .
PubMed: 38819167
DOI: 10.1128/jcm.00369-24 -
MSphere Jun 2024is the leading cause of severe mold infections in immunocompromised patients. This common fungus possesses innate attributes that allow it to evade the immune system,...
is the leading cause of severe mold infections in immunocompromised patients. This common fungus possesses innate attributes that allow it to evade the immune system, including its ability to survive the high copper (Cu) levels in phagosomes. Our previous work has revealed that under high Cu levels, the transcription factor AceA is activated, inducing the expression of the copper exporter CrpA to expel excess Cu. To identify additional elements in Cu resistance, we evolved wild-type and mutant Δ or Δ strains under increasing Cu concentrations. Sequencing of the resultant resistant strains identified both shared and unique evolutionary pathways to resistance. Reintroduction of three of the most common mutations in genes encoding Pma1 (plasma membrane H-ATPase), Gcs1 (glutamate cysteine-ligase), and Cpa1 (carbamoyl-phosphate synthetase), alone and in combination, into wild-type confirmed their additive role in conferring Cu resistance. Detailed analysis indicated that the mutation L424I preserves Pma1 H-ATPase activity under high Cu concentrations and that the mutation A37V confers a survival advantage to conidia in the presence of Cu. Interestingly, simultaneous mutations of all three genes did not alter virulence in infected mice. Our work has identified novel Cu-resistance pathways and provides an evolutionary approach for dissecting the molecular basis of adaptation to diverse environmental challenges.IMPORTANCE is the most common mold infecting patients with weakened immunity. Infection is caused by the inhalation of mold spores into the lungs and is often fatal. In healthy individuals, spores are engulfed by lung immune cells and destroyed by a combination of enzymes, oxidants, and high levels of copper. However, the mold can protect itself by pumping out excess copper with specific transporters. Here, we evolved under high copper levels and identified new genetic mutations that help it resist the toxic effects of copper. We studied how these mutations affect the mold's ability to resist copper and how they impact its ability to cause disease. This is the first such study in a pathogenic mold, and it gives us a better understanding of how it manages to bypass our body's defenses during an infection.
Topics: Aspergillus fumigatus; Copper; Animals; Mice; Fungal Proteins; Aspergillosis; Mutation; Drug Resistance, Fungal; Virulence; Evolution, Molecular; Glutamate-Cysteine Ligase; Female; Proton-Translocating ATPases
PubMed: 38814077
DOI: 10.1128/msphere.00253-24 -
Mycology 2024Asexual spores, called conidia, are key reproductive fungal particles that enable survival in harsh environmental conditions or host systems. The conidia can infect...
Asexual spores, called conidia, are key reproductive fungal particles that enable survival in harsh environmental conditions or host systems. The conidia can infect humans, animals, and plants to cause various fungal diseases. Transcription factors, including VosA, WetA, and SscA, have key roles in conidia formation and long-term survival in . Herein, we report the pleiotropic functions of SscA in the conidia of the human pathogen . The deletion of increased conidia formation despite decreased fungal growth. Absence of impaired long-term survival and reduced spore resistance to various stresses, including heat, UV, and oxidation. Transcriptomic analyses showed that SscA involved the mRNA expression of cell wall organisation-related genes. Importantly, the deletion mutant conidia contained an increased amount of β-glucan and chitin compared to wild type conidia. In addition, conidial gliotoxin production was decreased in the deletion strain. Overall, SscA has pleiotropic roles in conidia formation, maturation and dormancy and mycotoxin production in .
PubMed: 38813476
DOI: 10.1080/21501203.2023.2294061 -
Cureus Apr 2024Fosmanogepix, a prodrug of Manogepix (MGX), is a groundbreaking antifungal agent with broad-spectrum activity against yeasts, including and , as well as molds. It... (Review)
Review
Fosmanogepix, a prodrug of Manogepix (MGX), is a groundbreaking antifungal agent with broad-spectrum activity against yeasts, including and , as well as molds. It exhibits effectiveness against drug-resistant strains, such as strains resistant to and strains resistant to azoles. Furthermore, fosmanogepix shows activity against pathogens that typically resist other classes of drugs, such as , , and , although its efficacy against Mucorales varies. In animal models, fosmanogepix has demonstrated notable effectiveness against disseminated infections caused by various species, , and . It has also shown efficacy in pulmonary infection models involving , , , , and . Clinical trials have revealed excellent oral bioavailability (>90%), enabling a seamless transition between intravenous and oral formulations without compromising blood concentrations. Fosmanogepix exhibits favorable profiles in terms of drug interactions, tolerability, and extensive distribution in various tissues, making it an appealing choice for treating invasive fungal infections. This comprehensive review aims to examine the outcomes of published data on fosmanogepix, encompassing in vitro, in vivo, and clinical investigations.
PubMed: 38807795
DOI: 10.7759/cureus.59210 -
Infection and Drug Resistance 2024The role of -specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also...
BACKGROUND
The role of -specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also limited.
PURPOSE
This study aims to evaluate the quantitative test value of -specific IgG antibody in non-neutropenic IPA, which could provide additional evidence for related clinical diagnosis.
METHODS
This prospective study collected clinical data of suspected IPA patients from January, 2020 to December, 2022, and patients were divided into two groups, IPA and non-IPA. The study analyzed clinical characteristics and diagnostic value of -specific IgG antibody test, using the receiver operating characteristic (ROC) curve to evaluate diagnostic efficacy.
RESULTS
The study enrolled 59 IPA cases and 68 non-IPA cases, the average admission age of IPA group was 63.2±9.6 (33-79), and the gender ratio (male:female) of IPA group was 42:17. The proportion of patients with history of smoking and COPD were higher in IPA group (59.3% vs 39.7%, =0.027; 33.9% vs 14.7%, =0.011, respectively). The level of -specific IgG antibody in IPA group was significantly higher than non-IPA group (202.1±167.0 vs 62.6±58.0, <0.001). The area under the ROC curve was 0.799 (95%CI: 0.718, 0.865 <0.001), and the cut-off with best diagnostic efficacy was 91 AU/mL.
CONCLUSION
Immunological test plays an important role in the diagnosis of pulmonary aspergillosis, and -specific IgG antibody test has the good diagnostic value in non-neutropenic IPA.
PubMed: 38803521
DOI: 10.2147/IDR.S460513 -
Infection May 2024We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months.
OBJECTIVES
We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months.
METHODS
Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation.
RESULTS
Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles.
CONCLUSION
We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.
PubMed: 38801514
DOI: 10.1007/s15010-024-02236-7 -
Journal of Inflammation Research 2024To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5...
OBJECTIVE
To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM).
METHODS
A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared.
RESULTS
Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (>0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels ( all<0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, =0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with ( all<0.05).
CONCLUSION
IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors.
PubMed: 38800596
DOI: 10.2147/JIR.S460702 -
The World Allergy Organization Journal May 2024Fungi are known for their ability to cause allergies, but data on individual sensitization to them are insufficient. The purpose of the study was to carry out a...
BACKGROUND
Fungi are known for their ability to cause allergies, but data on individual sensitization to them are insufficient. The purpose of the study was to carry out a comprehensive analysis of the fungal allergens' sensitization profile in the Ukrainian population and to determine both population and individual sensitivity to these allergens.
METHODS
We utilized a set of ALEX allergy test data from 20,033 inhabitants of 17 regions of Ukraine from 1 to 89 years conducted in 2020-2022. A complex of programs in the Python language was developed and Bayesian network analysis was applied to determine the sensitivity combinations in individual patients to various fungal components.
RESULTS
Sensitivity to Alt a 1 dominated and was observed in 79.39% of patients, and 62.17% of them were sensitive solely to Alt a 1. Exclusive sensitivity to Mala s 6 was second in individual patient profiles with a frequency of 4.06%. Combined sensitivity to Alt a 1 - Asp f 3 was third with a share of 3.28%. Pen ch and Cla h extracts stimulated the production of the lowest median sIgE levels. The highest median sIgE levels were for Alt a 1, Mala s 11 and Asp f 6, respectively. Median sIgE levels increased in adults compared to children for all components of , as well as for Mala s 5 and Mala s 11. In the rest of the cases, they decreased in adults compared to children. The sensitization rates to fungi in general and specifically to were lower in the western parts of Ukraine, especially in the Carpathian region, situated within the Broad-leaved Forest zone. The results of Bayesian modeling revealed that in the case of Alt a 1, the simultaneous absence of sensitivity to Cla h 8, Mala s 11, Mala s 5 and Mala s 6 molecules could condition the presence of sensitization to the major allergen with a probability of 92.42%. In all other cases, there was a high probability of absence of sensitivity to particular allergen against the background of absence of sensitivity to other ones, which may indicate the independent development of sensitization to different fungal allergens.
CONCLUSIONS
Sensitivity to Alt a 1 dominated in the studied population with a lower rate in the western regions. The highest median sIgE levels were induced by Alt a 1, Mala s 11 and Asp f 6. Bayesian Analysis suggest a high probability of the independent development of sensitization to different fungal allergens. The idea that sensitization to one allergen may be protective against sensitization to another one(s) requires further clinical study.
PubMed: 38800499
DOI: 10.1016/j.waojou.2024.100908 -
Saudi Journal of Biological Sciences Jul 2024The inorganic colour layer based on iron oxide is affected by microorganisms (fungi) and leads to its deterioration due to feeding on the mineral elements through the...
The inorganic colour layer based on iron oxide is affected by microorganisms (fungi) and leads to its deterioration due to feeding on the mineral elements through the chemical composition of the colour in the presence of a suitable environment (medium). Damage occurs as a result of heavy metal elements being removed from the colour, leading to a defect in the chemical composition and the fading of the colours. The current study showed the effect of the different types of the most common fungi on oil paintings ( and ) after cultivating the different types of fungi and obtaining pure colonies for each fungus separately and conducting a fungal infection on experimental samples with preparing the old techniques, coloured with hematite red and goethite yellow. Each colour is mixed with different proportions of linseed oil (1, 2, 3). They were aged artificially and incubated at a temperature of 26 degrees and examined periodically until the fungi appeared on the surface in the form of colour spots ranging from very dark (severe infestation) to light (low infestation). The change in chemical composition was measured by Raman and EDX analyses of the samples before and after infection. Fungi showed the appearance of spoilage products from metal sulfides and metal carboxylates. The iron oxide ion decreased in both the red and the yellow colours, leading to a change after the fungal infection. Examination of the morphological surface using SEM, USB and measurement of colour change showed the change in the red colour more than the yellow and scattering of green and black colour dots on the surface of the sample. Correlation and Simple Linear Regression were applied for each colour before and after besides both colours together. It was found that these colours appeared around some of the fungal colonies as a result of the activities. Fungal species of some strains reduced Fe to Fe . This provides new insights into the role of microorganisms in the deterioration of painted surfaces.
PubMed: 38799718
DOI: 10.1016/j.sjbs.2024.104004 -
Experimental Eye Research Jul 2024Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory....
Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1β, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK.
Topics: Depsides; Rosmarinic Acid; Animals; Autophagy; Aspergillus fumigatus; Mice; Aspergillosis; Eye Infections, Fungal; Macrophages; Cinnamates; Reactive Oxygen Species; Membrane Potential, Mitochondrial; Keratitis; Disease Models, Animal; RAW 264.7 Cells; Cytokines; Phagocytosis
PubMed: 38797260
DOI: 10.1016/j.exer.2024.109944