Biology subjects

Momany, M.

Publications and source records attributed to Momany, M..

12 recordsLinked to original sources

bioRxiv2026

Temperature during Aspergillus fumigatus conidiophore development primes spore transcriptome for asexual, parasexual or sexual development

Aspergillus fumigatus is a thermotolerant saprobe found in soils and plant debris worldwide and an important pathogen of humans causing two million deaths annually. A. fumigatus makes abundant asexual spores (conidia) which are widely distributed by wind and can be inhaled from the environment. In susceptible individuals inhaled conidia break dormancy, germinate and grow in the lung leading to serious disease. Recent work has shown that conidia made at 37{degrees}C and 50{degrees}C have different morphologies and germination kinetics. While the asexual cycle is well-characterized at 37{degrees}C, much less is known about the asexual cycle at 50{degrees}C. Here, we combine flow cytometry and transcriptomics to track morphology and gene expression in the hyphae, conidiophores and conidia of A. fumigatus during asexual development at 37{degrees}C or 50{degrees}C. We show that the temperature during a narrow time window in late-stage conidiophore development dictates resulting conidial morphology, transcriptional program, and germination kinetics. As expected, conidiation at 37{degrees}C resulted in upregulation of brlA, the master regulator of asexual development, and its downstream targets in conidiophores and conidia. Surprisingly, conidiation at 50{degrees}C resulted in upregulation of MAT1-1, the master regulator of sexual development and its downstream targets in conidiophores and conidia. Our findings suggest that temperature during late conidiophore development transcriptionally primes conidia for asexual, parasexual or sexual development enhancing chances of survival for progeny. Our findings are especially relevant for agricultural compost where a wide gradient of temperatures exists, abundant A. fumigatus has been isolated, and resistance to antifungals is thought to evolve. IMPORTANCEThe human pathogen Aspergillus fumigatus has been found in natural and agricultural environments around the world. Disease is acquired when susceptible individuals inhale airborne asexual spores from the environment, which in agriculture generally includes proximity to compost and plant debris piles. This work shows that the environmental temperature when A. fumigatus spores are made determines the transcriptomes of those spores, priming them for future asexual or sexual development. The survival of asexual and sexual spores is very different at different temperatures, so these results are important for understanding how this pathogen survives in varied hostile environments. In addition, there are very few antifungal drugs with which to treat A. fumigatus infections, and resistance is increasing driven in part by agricultural use of fungicides. These results suggest that higher temperatures during asexual spore formation can lead to increased sexual reproduction and greater chances to evolve antifungal resistance.

microbiology↗

bioRxiv2025

Low level contamination confounds population genomic analysis

Genome sequence contamination has a variety of causes and can originate from within or between species. Previous research focused primarily on cross-species contamination or on prokaryotes. This paper visualizes B-allele frequency to test for intra-species contamination, and measures its effects on phylogenetic and admixture analysis in two fungal species. Using a standard base calling pipeline, we found that contaminated genomes superficially appeared to produce good quality genome data. Yet as little as 5-10% genome contamination was enough to change phylogenetic tree topologies and make contaminated strains appear as hybrids between lineages (genetically admixed). We recommend the use of B-allele frequency plots to screen genome resequencing data for intra-species contamination.

genomics↗

bioRxiv2024

Comparative Analysis of Polysaccharide and Cell Wall Structure in Aspergillus nidulans and Aspergillus fumigatus by Solid-State NMR

Invasive aspergillosis poses a significant threat to immunocompromised patients, leading to high mortality rates associated with these infections. Targeting the biosynthesis of cell wall carbohydrates is a promising strategy for antifungal drug development and will be advanced by a molecular-level understanding of the native structures of polysaccharides within their cellular context. Solid-state NMR spectroscopy has recently provided detailed insights into the cell wall organization of Aspergillus fumigatus, but genetic and biochemical evidence highlights species-specific differences among Aspergillus species. In this study, we employed a combination of 13C, 15N, and 1H-detection solid-state NMR, supplemented by Dynamic Nuclear Polarization (DNP), to compare the structural organization of cell wall polymers and their assembly in the cell walls of A. fumigatus and A. nidulans, both of which are key model organisms and human pathogens. The two species exhibited a similar rigid core architecture, consisting of chitin, -glucan, and {beta}-glucan, which contributed to comparable cell wall properties, including polymer dynamics, water retention, and supramolecular organization. However, differences were observed in the chitin, galactosaminogalactan, protein, and lipid content, as well as in the dynamics of galactomannan and the structure of the glucan matrix.

biophysics↗

bioRxiv2024

Widely dispersed clonal expansion of multi-fungicide-resistant Aspergillus fumigatus limits genomic epidemiology prospects

BackgroundAspergillus fumigatus is a ubiquitous fungus that causes a range of diseases in animals, including humans. The most lethal manifestation is invasive aspergillosis for which treatment relies on triazoles. Triazole-resistant A. fumigatus can be recovered from decaying plant material and so-called hotspots containing triazole fungicide residues. Although observations have shown clonal isolates between the environment and clinical samples, a direct link between a specific environment and cases of triazole-resistant invasive aspergillus disease in an individual patient has not yet been demonstrated. MethodsTo understand where patients acquire A. fumigatus isolates causing disease, we used a genomic epidemiology approach with 157 Dutch A. fumigatus isolates, based on whole genome sequencing. Isolates were from three well-characterized environmental hotspots and two hospitals between 2016 and 2019. FindingsIn the Dutch dataset, A. fumigatus isolates from six patients showed near-identical genomes compared to five environmental isolates. One environmental isolate matched three probable cases of triazole-resistant invasive aspergillosis, including one fatal case. Patient isolates were recovered up to 34 months later than near-identical environmental isolates. Comparison to over 1{middle dot}2K global publicly available A. fumigatus genomes showed hundreds of clonal groups spread across three continents. In addition, finding variants associated with resistance to non-triazole fungicides such as benzimidazole, succinate dehydrogenase inhibitor and quinone outside inhibitor classes, strongly suggests an exposure history to multiple agricultural fungicides in these environmental hotspots. InterpretationEnvironmental hotspots represent highly selective habitats for multi-fungicide-resistant A. fumigatus, which we can now directly link to probable cases of aspergillus disease, including a triazole-resistant case. However, geographically widely dispersed clonal expansion limits the utility of genomic epidemiology to identify the source of a particular patients isolate. Furthermore, reducing a single class of fungicides in agriculture may not effectively reduce resistance selection when other classes are still in use. FundingNWO.Groen2019.002 Research in contextO_ST_ABSEvidence before this studyC_ST_ABSTriazole fungicides that exhibit activity against Aspergillus fumigatus have been shown to be a major source of resistant aspergillus disease in humans. However, the route of transmission from environmental hotspot to human remains poorly understood. Isolates of A. fumigatus can be recovered from both environmental samples and clinical specimens that harbour the same resistance signature haplotypes, e.g., TR34/L98H and TR46/Y121F/T289A, in the cyp51A-gene. We searched the literature for evidence using high resolution whole genome sequencing (WGS) to link environmental isolates to human infection. We searched PubMed for articles using the search terms Aspergillus fumigatus AND azole resistance AND whole genome sequencing on 15 April 2024. This search retrieved 32 articles describing different evolutionary routes to select for triazole-resistant A. fumigatus or population structure of whole-genome sequenced isolates. Twenty-six articles used whole-genome sequencing, but none focused on identifying clonal groups to identify direct cases of transmission between the environment and clinical cases of aspergillus disease. By using the additional search term transmission, no other records were retrieved. Added value of this studyOur study links triazole-resistant A. fumigatus isolates cultured from three environmental hotspots to cases of aspergillus disease in two hospitals in the Netherlands. Genome comparisons of isolates from environmental hotspots and patients showed multiple near-identical linked genotypes, consistent with a route of transmission from the environment to patients. Although a naive expectation may be a higher probability of matches of the hotspots located in the northwest of the Netherlands with the hospital located in the west of the country, in fact, more patient isolates from the far southeast were linked to the hotspots. Integrating the Dutch data set into a global data set showed 205 clonal groups spread across the Netherlands, Germany, the United Kingdom (UK), the United States of America (USA) and Japan. Our demonstration of a large number of geographically dispersed clonal groups suggests that current sampling is insufficient to definitively identify the source of an individual patients infection. A genetically highly diverse population combined with a wide global distribution of clones can make it impossible to definitively identify the source of an individual patients infection even with much more sampling. Implications of all the available evidenceOur study provides evidence that triazole-resistant A. fumigatus isolates with multi-fungicide resistance profiles cause aspergillus disease in at-risk patients and may contribute to treatment failure and mortality. The risk of infection due to these triazole-resistant isolates is not confined to the geographic vicinity of the environmental hotspot since clonal spread can be detected across great distances. The finding of linked cases without clear transmission routes limits epidemiological studies and underscores the need to better understand the ecology and environmental niches of this fungus. As it is highly unlikely that each patient visited the rural agricultural areas where a hotspot was located, research should address the complex and long-distance transmission routes of resistant isolates, which involves airborne dispersal of conidia or habitats of this fungus outside the agricultural environment. Furthermore, because of the multi-fungicide resistance phenotype of the triazole-resistant A. fumigatus, involving several classes of fungicides, reducing one class of fungicides in the environment may not effectively reduce resistance selection. Effective interventions should instead aim to reduce the burden of environmental resistance by modifying environments that currently favour the massive outgrowth of fungicide-resistant A. fumigatus to limit the escape of aerial spores from these environmental hotspots.

microbiology↗

bioRxiv2024

The Evolutionary Origins and Ancestral Features of Septins

Septins are a family of membrane-associated cytoskeletal GTPases that play crucial roles in various cellular processes, such as cell division, phagocytosis, and organelle fission. Despite their importance, the evolutionary origins and ancestral function of septins remain unclear. In opisthokonts, septins form five distinct groups of orthologs, with subunits from multiple groups assembling into heteropolymers, thus supporting their diverse molecular functions. Recent studies have revealed that septins are also conserved in algae and protists, indicating an ancient origin from the last eukaryotic common ancestor. However, the phylogenetic relationships among septins across eukaryotes remained unclear. Here, we expanded the list of non-opisthokont septins, including previously unrecognized septins from rhodophyte red algae and glaucophyte algae. Constructing a rooted phylogenetic tree of 254 total septins, we observed a bifurcation between the major non-opisthokont and opisthokont septin clades. Within the non-opisthokont septins, we identified three major subclades: Group 6 representing chlorophyte green algae (6A mostly for species with single septins, 6B for species with multiple septins), Group 7 representing algae in chlorophytes, heterokonts, haptophytes, chrysophytes, and rhodophytes, and Group 8 representing ciliates. Glaucophyte and some ciliate septins formed orphan lineages in-between all other septins and the outgroup. Combining ancestral-sequence reconstruction and AlphaFold predictions, we tracked the structural evolution of septins across eukaryotes. In the GTPase domain, we identified a conserved GAP-like arginine finger within the G-interface of at least one septin in most algal and ciliate species. This residue is required for homodimerization of the single Chlamydomonas septin, and its loss coincided with septin duplication events in various lineages. The loss of the arginine finger is often accompanied by the emergence of the 0 helix, a known NC-interface interaction motif, potentially signifying the diversification of septin-septin interaction mechanisms from homo-dimerization to hetero-oligomerization. Lastly, we found amphipathic helices in all septin groups, suggesting that curvature-sensing is an ancestral trait of septin proteins. Coiled-coil domains were also broadly distributed, while transmembrane domains were found in some septins in Group 6A and 7. In summary, this study advances our understanding of septin distribution and phylogenetic groupings, shedding light on their ancestral features, potential function, and early evolution.

cell biology↗

bioRxiv2023

Pan-azole- and multi-fungicide-resistant Aspergillus fumigatus is widespread in the United States

Aspergillus fumigatus is an important global fungal pathogen of humans. Azole drugs are among the most effective treatments for A. fumigatus infection. Azoles are also widely used in agriculture as fungicides against fungal pathogens of crops. Azole-resistant A. fumigatus has been increasing in Europe and Asia for two decades where clinical resistance is thought to be driven by agricultural use of azole fungicides. The most prevalent mechanisms of azole resistance in A. fumigatus are tandem repeats (TR) in the cyp51A promoter coupled with mutations in the coding region which result in resistance to multiple azole drugs (pan-azole resistance). Azole-resistant A. fumigatus has been isolated from patients in the United States (U.S.), but little is known about its environmental distribution. To better understand the distribution of azole-resistant A. fumigatus in the U.S., we collected isolates from agricultural sites in 8 states and tested 202 isolates for sensitivity to azoles. We found azole-resistant A. fumigatus in agricultural environments in 7 states showing that it is widespread in the U.S. We sequenced environmental isolates representing the range of U.S. sample sites and compared them with publicly available environmental worldwide isolates in phylogenetic, principal component, and ADMIXTURE analyses. We found worldwide isolates fell into three clades and that TR-based pan-azole resistance was largely in a single clade that was strongly associated with resistance to multiple agricultural fungicides. We also found high levels of gene flow with clear recombination between two clades highlighting the potential for azole-resistance to continue spreading in the U.S. ImportanceAspergillus fumigatus is a fungal pathogen of humans that causes over 250,000 invasive infections each year. It is found in soils, plant debris and compost. Azoles are the first line of defense antifungal drugs against A. fumigatus. Azoles are also used as agricultural fungicides to combat other fungi that attack plants. Azole-resistant A. fumigatus has been a problem in Europe and Asia for twenty years and has recently been reported in patients in the U.S. Until this study we didnt know much about azole-resistant A. fumigatus in agricultural settings in the U.S. In this study we isolated azole-resistant A. fumigatus from multiple states and compared it to isolates from around the world. We show that A. fumigatus that is resistant to azoles and to other strictly agricultural fungicides is widespread in the U.S.

microbiology↗

bioRxiv2023

Elevated mutation rates in the multi-azole resistant Aspergillus fumigatus cladedrives rapid evolution of antifungal resistance

The evolution of antifungal resistance is an emerging global threat. Particularly concerning is the widespread occurrence of azole resistance within Aspergillus fumigatus, a globally ubiquitous environmental mould that causes over 1 million life-threatening invasive infections in humans each year. It is increasingly evident that the environmental use of azoles has led to selective sweeps across multiple genomic loci resulting in the rapid expansion of a genetically distinct cluster of genotypes (clade A) that results in resistance to clinically deployed azoles. Isolates within this cluster are more likely to be cross resistant to agricultural antifungals with unrelated modes of action suggesting they may be adapting rapidly to antifungal challenge. Here we show that this cluster is not only multi-azole resistant but has increased propensity to develop resistance to new antifungals because of variants in the DNA mismatch repair system. A variant in msh6 is found almost exclusively within clade A, occurs in 88% of multi-azole resistant isolates harbouring the canonical cyp51A azole resistance allelic variant TR34/L98H, and is globally distributed. Naturally occurring isolates with this msh6 variant display a 4 to 9-times higher rate of mutation, leading to an increased propensity to evolve resistance to current and next generation antifungals. We argue that pervasive environmental use of fungicides creates selective arenas whereby genotypes of A. fumigatus with increased adaptive capability thrive in the face of strong directional selection, leading to the genesis and amplification of antifungal resistance. These results help explain the pronounced clustering of multiple independent resistance mechanisms within the mutable clade A. Our findings further suggest that resistance to next generation antifungals is more likely to emerge within organisms that are already multi-azole resistant, posing a major problem due to the prospect of dual use of novel antifungals in clinical and agricultural settings.

microbiology↗

bioRxiv2022

Analysis of Cyp51 protein sequences shows 4 major Cyp51 gene family groups across Fungi

Azole drugs target fungal sterol biosynthesis and are used to treat millions of human fungal infections each year. Resistance to azole drugs has emerged in multiple fungal pathogens including Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum, and Aspergillus fumigatus. The most well-studied resistance mechanism in A. fumigatus arises from missense mutations in the coding sequence combined with a tandem repeat in the promoter of cyp51A, which encodes a cytochrome P450 enzyme in the fungal sterol biosynthesis pathway. Filamentous members of Ascomycota such as A. fumigatus have either one or two of three Cyp51 paralogs (Cyp51A, Cyp51B, and Cyp51C). Most previous research in A. fumigatus has focused on Cyp51A due to its role in azole resistance. We used the A. fumigatus Cyp51A protein sequence as the query in database searches to identify Cyp51 proteins across Fungi. We found 435 Cyp51 proteins in 301 species spanning from early-diverging fungi (Blastocladiomycota, Chytridiomycota, Zoopagomycota and Mucormycota) to late-diverging fungi (Ascomycota and Basidiomycota). We found these sequences formed 4 major Cyp51 groups: Cyp51, Cyp51A, Cyp51B, and Cyp51C. Surprisingly, we found all filamentous Ascomycota had a Cyp51B paralog, while only 50% had a Cyp51A paralog. We created maximum likelihood trees to investigate the evolution of Cyp51 in Fungi. Our results suggest Cyp51 is present in all fungi with three paralogs emerging in Pezizomycotina, including Cyp51C which appears to have diverged from the progenitor of the Cyp51A and Cyp51B groups. Author SummaryEach year millions of people are infected by a fungal pathogen and receive antifungal treatment with azole drugs. Resistance to azole drugs is becoming increasingly prevalent and is mostly caused by mutations in the azole drug target, Cyp51. Aspergillus fumigatus is an airborne fungal pathogen that causes more than 600,000 deaths every year. Azole resistance in A. fumigatus is primarily driven by a promoter repeat coupled with mutations in cyp51A. In our study, we found 435 Cyp51 proteins in 4 major groups across Fungi, with some species having multiple Cyp51 proteins (Cyp51, Cyp51A, Cyp51B, and Cyp51C). Although most research in A. fumigatus has focused on Cyp51A, we found Cyp51B in all filamentous Ascomycota fungi showing it is more conserved than Cyp51A and likely plays a vital role in these fungi. Author Summary (Shortened)Resistance to azole drugs is becoming increasingly prevalent and is mostly caused by mutations in the azole drug target, Cyp51. Azole resistance in Aspergillus fumigatus is primarily driven by a promoter repeat coupled with mutations in cyp51A. We found 435 Cyp51 proteins in 4 major groups across Fungi, with some species having multiple Cyp51 proteins (Cyp51, Cyp51A, Cyp51B, and Cyp51C). Although most research focuses on Cyp51A, we found Cyp51B in all filamentous Ascomycota fungi showing its more conserved than Cyp51A.

microbiology↗

bioRxiv2020

Evidence for the agricultural origin of antimicrobial resistance in a fungal pathogen of humans

Resistance to clinical antimicrobials is an urgent problem, reducing our ability to combat deadly pathogens of humans. Azole antimicrobials target ergosterol synthesis and are highly effective against fungal pathogens of both humans and plants leading to their widespread use in clinical and agricultural settings1,2. The fungus Aspergillus fumigatus causes 300,000 life-threatening infections in susceptible human hosts annually and azoles are the most effective treatment3. Resistance to clinical azole antifungals has become a major problem in Europe and India over the last decade, where identical mutations in cyp51A, an ergosterol biosynthetic gene, have been found in strains from both clinical and agricultural settings4. Shared cyp51A genotypes suggest that clinical azole resistance might have had an agricultural origin; however, until now, independent origins of clinical and agricultural mutations could not be ruled out. Here we show that azole-resistant isolates of A. fumigatus from clinical and agricultural settings also carry mutations conferring resistance to quinone outside inhibitor (QoI) fungicides, which are used exclusively in agricultural settings. This is the first report of a clear marker for the agricultural origin of resistance to a clinical antifungal. We anticipate that our work will increase the understanding of interactions between pathogens of plants and pathogens of humans.

microbiology↗

bioRxiv2020

Septins coordinate cell wall integrity and lipid metabolism in a sphingolipid-dependent process

During normal development and response to environmental stress, fungi must coordinate synthesis of the cell wall and plasma membrane. Septins, small cytoskeletal GTPases, colocalize with membrane sterol-rich regions and facilitate recruitment of cell wall synthases during dynamic wall remodeling. In this study we show that null mutants missing an Aspergillus nidulans core septin present in hexamers and octamers ({Delta}aspAcdc11, {Delta}aspBcdc3, or {Delta}aspCcdc12) are sensitive to multiple cell wall-disturbing agents known to activate the cell wall integrity MAPK pathway and that this sensitivity can be remediated by osmotic support. The null mutant missing the octamer-exclusive core septin ({Delta}aspDcdc10) showed similar osmotic-remedial sensitivity, but only to a single cell wall-disturbing agent and the null mutant missing the noncore septin ({Delta}aspE) showed very mild osmotic-remedial sensitivity to a different single agent. Representative core septin null mutants showed changes in cell wall polysaccharide composition, organization, and chitin synthase localization. Double mutant analysis with{Delta} mpkA suggested core septins interact with the cell wall integrity pathway. Null mutants missing any of the five septins were resistant to ergosterol-disrupting agents. The {Delta}aspAcdc11, {Delta}aspBcdc3, and {Delta}aspCcdc12 mutants showed increased sensitivity to sphingolipid-disrupting agents that was remediated by addition of exogenous phytosphingosine. Representative core septins were mislocalized after treatment with sphingolipid-disrupting agents, but not after treatment with ergosterol-disrupting agents. When challenged with both sphingolipid-disturbing and cell wall-disturbing agents in combination, remediation of the lipid defect restored proper growth to {Delta}aspAcdc11, {Delta}aspBcdc3, and {Delta}aspCcdc12, but remediation of the cell wall defect did not. Our data suggest that the core hexamer and octamer septins are involved in cell wall integrity signaling with the noncore septin playing a minor role; that all five septins are involved in monitoring ergosterol metabolism; that the hexamer septins are required for sphingolipid metabolism; and that septins require sphingolipids to coordinate the cell wall integrity response.

cell biology↗

bioRxiv2019

Sporulation environment drives phenotypic variation in the pathogen Aspergillus fumigatus

Aspergillus fumigatus causes more than 300,000 life-threatening infections annually and is widespread across varied environments with a single colony producing thousands of conidia, genetically-identical dormant spores. Conidia are easily wind-dispersed to new environments where they can germinate and, if inhaled by susceptible hosts, cause disease. Using high-throughput, single-cell analysis we show that germination phenotypes vary among genetically-identical individuals and that the environment of spore production determines the degree of germination heterogeneity.

microbiology↗

bioRxiv2019

Targeted antifungal liposomes

Aspergillus species cause pulmonary invasive aspergillosis resulting in nearly a hundred thousand deaths each year. Patients at the greatest risk of developing life-threatening aspergillosis have weakened immune systems and/or various lung disorders. Patients are treated with antifungals such as amphotericin B (AmB), casofungin acetate, or triazoles (itraconazole, voriconazole etc.), but these antifungal agents have serious limitations due to lack of sufficient fungicidal effect and human toxicity. Liposomes with AmB intercalated into the lipid membrane (AmBisomes, AmB-LLs), have several-fold reduced toxicity compared to detergent solubilized drug. However, even with the current antifungal therapies, one-year survival among patients is only 25 to 60%. Hence, there is a critical need for improved antifungal therapeutics.\n\nDectin-1 is a mammalian innate immune receptor in the membrane of some leukocytes that binds as a dimer to beta-glucans found in fungal cell walls, signaling fungal infection. Using a novel protocol, we coated AmB-LLs with Dectin-1s beta-glucan binding domain to make DEC-AmB-LLs. DEC-AmB-LLs bound rapidly, efficiently, and with great strength Aspergillus fumigatus and to Candida albicans and Cryptococcus neoformans, highly divergent fungal pathogens of global importance. By contrast, un-targeted AmB-LLs and BSA-coated BSA-AmB-LLs showed 200-fold lower affinity for fungal cells. DEC-AmB-LLs reduced the growth and viability of A. fumigatus an order of magnitude more efficiently than untargeted control liposomes delivering the same concentrations of AmB, in essence increasing the effective dose of AmB. Future efforts will focus on examining pan-antifungal targeted liposomal drugs in animal models of disease.\n\nTweetWe coated anti-fungal drug loaded liposomes to fungal cell walls with a beta-glucan binding protein and thereby increased drug effectiveness by an order of magnitude.\n\nImportanceThe fungus Aspergillus fumigatus causes pulmonary invasive aspergillosis resulting in nearly a hundred thousand deaths each year. Patients are often treated with antifungal drugs such as amphotericin B loaded into liposomes, AmB-LLs, but all antifungal drugs including AmB-LLs have serious limitations due to human toxicity and insufficient fungal cell killing. Even with the best current therapies, one-year survival among patients with invasive aspergillosis is only 25 to 60%. Hence, there is a critical need for improved antifungal therapeutics.\n\nDectin-1 is a mammalian protein that binds to beta-glucan polysaccharides found in nearly all fungal cell walls. We coated AmB-LLs with Dectin-1 to make DEC-AmB-LLs. DEC-AmB-LLs bond strongly to fungal cells, while AmB-LLs had little affinity. DEC-AmB-LLs killed or inhibited A. fumigatus ten times more efficiently than untargeted lipsomes, increasing the effective dose of AmB. Dectin-1 coated liposomes targeting fungal pathogens have the potential to greatly enhance antifungal therapeutics.

molecular biology↗