Published: Jan. 1, 2024
Language: Английский
Current Clinical Microbiology Reports, Journal Year: 2024, Volume and Issue: 11(2), P. 43 - 50
Published: March 18, 2024
Abstract Purpose of Review Over recent decades, the number outbreaks caused by fungi has increased for humans, plants (including important crop species) and animals. Yet this problem is compounded emerging antifungal drug resistance in pathogenic species. Resistance develops over time when are exposed to drugs either patient or environment. Recent Findings Novel resistant variants fungal pathogens that were previously susceptible evolving (such as Aspergillus fumigatus ) well newly species displaying profiles (e.g. Candida auris Trichophyton indotineae ). Summary This review highlights topic how it evolved, relates a growing public health burden.
Language: Английский
Citations
13
Microbiology and Molecular Biology Reviews, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 10, 2025
SUMMARY Advances in modern medical therapies for many previously intractable human diseases have improved patient outcomes. However, successful disease treatment outcomes are often prevented due to invasive fungal infections caused by the environmental mold Aspergillus fumigatus . As contemporary antifungal not experienced same robust advances as other therapies, defining mechanisms of A. initiation and progression remains a critical research priority. To this end, World Health Organization recently identified priority pathogen Centers Disease Control has highlighted emergence triazole-resistant isolates. The expansion diversity host populations susceptible aspergillosis complex dynamic genotypic phenotypic call reinvigorated assessment pathobiological drug-susceptibility mechanisms. Here, we summarize recent advancements field discuss challenges our understanding heterogeneity its pathogenesis diverse populations.
Language: Английский
Citations
1
Applied and Environmental Microbiology, Journal Year: 2024, Volume and Issue: 90(4)
Published: April 1, 2024
ABSTRACT Aspergillus fumigatus is an important global fungal pathogen of humans. Azole drugs are among the most effective treatments for A. infection. Azoles also widely used in agriculture as fungicides against pathogens crops. Azole-resistant has been increasing Europe and Asia two decades where clinical resistance thought to be driven by agricultural use azole fungicides. The prevalent mechanisms tandem repeats (TR) cyp51A promoter coupled with mutations coding region which result multiple (pan-azole resistance). isolated from patients United States (U.S.), but little known about its environmental distribution. To better understand distribution azole-resistant U.S., we collected isolates sites eight states tested 202 sensitivity azoles. We found environments seven showing that it widespread U.S. sequenced representing range sample compared them publicly available worldwide phylogenetic, principal component, ADMIXTURE analyses. fell into three clades, TR-based pan-azole was largely a single clade strongly associated high levels gene flow indicating recombination between clades highlighting potential azole-resistance continue spreading IMPORTANCE humans causes over 250,000 invasive infections each year. It soils, plant debris, compost. first line defense antifungal . combat other fungi attack plants. problem 20 years recently reported (U.S.). Until this study, did not know much settings In around world. show resistant azoles strictly
Language: Английский
Citations
7
Seminars in Respiratory and Critical Care Medicine, Journal Year: 2024, Volume and Issue: 45(01), P. 032 - 040
Published: Jan. 9, 2024
Abstract Aspergilli may cause various pulmonary diseases in humans, including allergic bronchopulmonary aspergillosis (ABPA), chronic (CPA), and acute invasive (IPA). In addition, colonization occur cystic fibrosis (CF). Aspergillus fumigatus represents the main pathogen, which employ different morphotypes, for example, conidia, hyphal growth, asexual sporulation, diseases. These morphotypes determine ease by A. can adapt to stress antifungal drug exposure, usually resulting one or more resistance mutations. Key factors that enable emergence of include genetic variation selection. The ability create depends on reproduction mode, including, sexual, parasexual, asexual, population size. cycles take place host and/or environment, when specific conditions are present. Environmental is commonly characterized tandem repeat (TR)-mediated mutations, while in-host selection results single-resistance Reported cases from literature indicate environmental mutations almost exclusively present patients with IA indicating risk very low. aspergilloma, single-point dominant genotype, other diseases, ABPA, CPA, CF, both TR-mediated reported. Insights into pathogenesis help improve diagnostic therapeutic strategies.
Language: Английский
Citations
4
Molecular Biology and Evolution, Journal Year: 2024, Volume and Issue: 41(5)
Published: April 23, 2024
Abstract In fungi, fusion between individuals leads to localized cell death, a phenomenon termed heterokaryon incompatibility. Generally, the genes responsible for this incompatibility are observed be under balancing selection resulting from negative frequency-dependent selection. Here, we assess in Aspergillus fumigatus, human pathogenic fungus with very low level of linkage disequilibrium as well an extremely high crossover rate. Using complementation auxotrophic mutations assay hyphal compatibility, screened sexual progeny compatibility identify involved process, called het genes. total, 5/148 (3.4%) offspring were compatible parent and 166/2,142 (7.7%) sibling pairs compatible, consistent several segregating loci. Genetic mapping identified five loci, four which could fine mapped individual genes, tested three through heterologous expression, confirming their causal relationship. Consistent long-term selection, trans-species polymorphisms apparent across sister species, equal allele frequencies within A. fumigatus. Surprisingly, sliding window genome-wide population-level analysis independent dataset did not show increased Tajima's D near these contrast what is often found surrounding loci available de novo assemblies, that balanced restricted hundred base flanking coding sequence. addition identifying first work highlights interaction rapid decay.
Language: Английский
Citations
4
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Dec. 16, 2024
The environmental use of azole fungicides has led to selective sweeps across multiple loci in the Aspergillus fumigatus genome causing rapid global expansion a genetically distinct cluster resistant genotypes. Isolates within this are also more likely be agricultural antifungals with unrelated modes action. Here we show that is not only multi-azole but increased propensity develop resistance next generation because variants DNA mismatch repair system. A variant msh6-G233A found almost exclusively isolates harbouring canonical cyp51A allelic TR34/L98H. Naturally occurring msh6 display up 5-times higher rate mutation, leading an likelihood evolving other antifungals. Furthermore, unlike hypermutator strains, G233A conveys no measurable fitness cost and become globally distributed. Our findings further suggest next-generation emerge organisms already due close linkage between TR34/L98H msh6-G233A, posing major problem prospect dual novel clinical settings.
Language: Английский
Citations
4
PLoS Genetics, Journal Year: 2025, Volume and Issue: 21(4), P. e1011669 - e1011669
Published: April 15, 2025
Elucidating the genomic architecture of quantitative traits is essential for our understanding adaptation and breeding in domesticated organisms. Penicillium roqueforti mold used worldwide blue cheese maturation, contributing to flavors through proteolytic lipolytic activities. The two populations display very little genetic diversity, but are differentiated carry opposite mating types. We produced haploid F1 progenies from five crosses, using parents belonging non-cheese populations. Analyses high-quality genome assemblies parental strains revealed large translocations, having occurred via a circular intermediate, one with footprints Starship giant mobile elements. Offspring genotyping genotype-by-sequencing (GBS) several regions segregation distortion, possibly linked degeneration lineages. found transgressions relevant making, offspring more extreme trait values than strains. identified loci (QTLs) colony color, lipolysis, proteolysis, extrolite production, including mycotoxins, not growth rates. Some appeared rich QTLs both lipid protein metabolism, other production multiple extrolites, indicating that have pleiotropic effects. corresponded known biosynthetic gene clusters, e.g., melanin or extrolites. hybrids constitute valuable producers, new allelic combinations, allowed identifying target important paving way strain improvement. findings further contribute mechanisms underlying rapid adaptation, revealing convergent targeting major regulators.
Language: Английский
Citations
0
Current Biology, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Members of the fungal kingdom serve as models for numerous cellular processes, among them sexuality.1 In heterothallic ascomycetes, mating-type systems ensure that only compatible isolates fuse to enter sexual phase.2,3,4,5,6 This includes reciprocal secretion and recognition pheromones, commonly termed α-factor a-factor, which are processed from peptide precursors.7,8,9,10 Identification mating pheromones their cognate receptors has been achieved by homology searches11,12,13,14,15,16,17; however, this approach had failed detect a-factor-like Eurotiomycetes,5,18,19,20,21 a group including medically economically important species.22 Sexuality opportunistic pathogen Aspergillus fumigatus23,24,25 is genetically determined bipolar system encoding MAT1-1-1 MAT1-2-1 regulators.16,26,27,28,29,30 By analyzing transcriptome data strains overexpressing corresponding MAT genes,31 we identified candidate pheromone precursor gene B (ppgB) encode elusive Eurotiomycete a-factor pheromone. Its deduced 24 aa in length features canonical CaaX farnesylation motif. Further analyses provided supporting evidence PpgB prototype aspergilli, expression ppgB MAT1-2-1-dependent manner, an A. fumigatus ppgBΔ deletion strain was unable mate form fruiting bodies with partner. Inspection genomes members section Fumigati revealed high conservation sequence well α-factor-like PpgA, indicating incompatibility factors other than solely discrimination responsible speciation. The identification fumigatusa-factor-like closes substantial knowledge gap respect propagation fungi.
Language: Английский
Citations
0
Nature Reviews Microbiology, Journal Year: 2025, Volume and Issue: unknown
Published: May 2, 2025
Language: Английский
Citations
0
iScience, Journal Year: 2023, Volume and Issue: 26(9), P. 107614 - 107614
Published: Aug. 11, 2023
In most eukaryotes, meiotic crossovers (COs) are limited to 1-3 per chromosome, and prevented from occurring close one another by CO interference. The fission yeast
Language: Английский
Citations
6