The HAP Complex Governs Fumonisin Biosynthesis and Maize Kernel Pathogenesis in Fusarium verticillioides

2016 ◽  
Vol 79 (9) ◽  
pp. 1498-1507 ◽  
Author(s):  
JOHN B. RIDENOUR ◽  
JONATHON E. SMITH ◽  
BURTON H. BLUHM
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Transcriptional Profiling ◽  
Fusarium Verticillioides ◽  
Consensus Sequence ◽  
Functional Characterization ◽  
Gene Clusters ◽  
Negative Regulator ◽  
Maize Production ◽  
Hap Complex

ABSTRACT Contamination of maize (Zea mays) with fumonisins produced by the fungus Fusarium verticillioides is a global concern for food safety. Fumonisins are a group of polyketide-derived secondary metabolites linked to esophageal cancer and neural tube birth defects in humans and numerous toxicoses in livestock. Despite the importance of fumonisins in global maize production, the regulation of fumonisin biosynthesis during kernel pathogenesis is poorly understood. The HAP complex is a conserved, heterotrimeric transcriptional regulator that binds the consensus sequence CCAAT to modulate gene expression. Recently, functional characterization of the Hap3 subunit linked the HAP complex to the regulation of secondary metabolism and stalk rot pathogenesis in F. verticillioides. Here, we determine the involvement of HAP3 in fumonisin biosynthesis and kernel pathogenesis. Deletion of HAP3 suppressed fumonisin biosynthesis on both nonviable and live maize kernels and impaired pathogenesis in living kernels. Transcriptional profiling via RNA sequencing indicated that the HAP complex regulates at least 1,223 genes in F. verticillioides, representing nearly 10% of all predicted genes. Disruption of the HAP complex caused the misregulation of biosynthetic gene clusters underlying the production of secondary metabolites, including fusarins. Taken together, these results reveal that the HAP complex is a central regulator of fumonisin biosynthesis and kernel pathogenesis and works as both a positive and negative regulator of secondary metabolism in F. verticillioides.

scholarly journals Biofilm Formation in Pseudomonas aeruginosa: Fimbrial cup Gene Clusters Are Controlled by the Transcriptional Regulator MvaT

2004 ◽  
Vol 186 (9) ◽  
pp. 2880-2890 ◽  
Author(s):  
Isabelle Vallet ◽  
Stephen P. Diggle ◽  
Rachael E. Stacey ◽  
Miguel Cámara ◽  
Isabelle Ventre ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Dna Microarrays ◽  
Transcriptional Profiling ◽  
Bacterial Pathogen ◽  
Gene Clusters ◽  
Northern Blotting ◽  
Negative Regulator ◽  
Regulatory Control ◽  
Homologous Gene

ABSTRACT Pseudomonas aeruginosa is an opportunistic bacterial pathogen which poses a major threat to long-term-hospitalized patients and individuals with cystic fibrosis. The capacity of P. aeruginosa to form biofilms is an important requirement for chronic colonization of human tissues and for persistence in implanted medical devices. Various stages of biofilm formation by this organism are mediated by extracellular appendages, such as type IV pili and flagella. Recently, we identified three P. aeruginosa gene clusters that were termed cup (chaperone-usher pathway) based on their sequence relatedness to the chaperone-usher fimbrial assembly pathway in other bacteria. The cupA gene cluster, but not the cupB or cupC cluster, is required for biofilm formation on abiotic surfaces. In this study, we identified a gene (mvaT) encoding a negative regulator of cupA expression. Such regulatory control was confirmed by several approaches, including lacZ transcriptional fusions, Northern blotting, and transcriptional profiling using DNA microarrays. MvaT also represses the expression of the cupB and cupC genes, although the extent of the regulatory effect is not as pronounced as with cupA. Consistent with this finding, mvaT mutants exhibit enhanced biofilm formation. Although the P. aeruginosa genome contains a highly homologous gene, mvaU, the repression of cupA genes is MvaT specific. Thus, MvaT appears to be an important regulatory component within a complex network that controls biofilm formation and maturation in P. aeruginosa.

scholarly journals IMG-ABC: A Knowledge Base To Fuel Discovery of Biosynthetic Gene Clusters and Novel Secondary Metabolites

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Michalis Hadjithomas ◽  
I-Min Amy Chen ◽  
Ken Chu ◽  
Anna Ratner ◽  
Krishna Palaniappan ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Genomic Data ◽  
Gene Clusters ◽  
Metagenomic Data ◽  
Integrated Analysis ◽  
Analysis Tool ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Analysis Tools

ABSTRACTIn the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of “big” genomic data for discovering small molecules. IMG-ABC relies on IMG's comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve as the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC's focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time inAlphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalable framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules.IMPORTANCEIMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG's extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to expand, with the goal of becoming an essential component of any bioinformatic exploration of the secondary metabolism world.

scholarly journals Characterizing the Pathogenic, Genomic, and Chemical Traits ofAspergillus fischeri, a Close Relative of the Major Human Fungal PathogenAspergillus fumigatus

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Matthew E. Mead ◽  
Sonja L. Knowles ◽  
Huzefa A. Raja ◽  
Sarah R. Beattie ◽  
Caitlin H. Kowalski ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Aspergillus Fumigatus ◽  
Secondary Metabolism ◽  
Human Disease ◽  
Chemical Characterization ◽  
Gene Clusters ◽  
Invasive Disease ◽  
Close Relative ◽  
Low Oxygen ◽  
Content Type

ABSTRACTAspergillus fischeriis closely related toAspergillus fumigatus, the major cause of invasive mold infections. Even thoughA. fischeriis commonly found in diverse environments, including hospitals, it rarely causes invasive disease. WhyA. fischericauses less human disease thanA. fumigatusis unclear. A comparison ofA. fischeriandA. fumigatusfor pathogenic, genomic, and secondary metabolic traits revealed multiple differences in pathogenesis-related phenotypes. We observed thatA. fischeriNRRL 181 is less virulent thanA. fumigatusstrain CEA10 in multiple animal models of disease, grows slower in low-oxygen environments, and is more sensitive to oxidative stress. Strikingly, the observed differences for some traits are of the same order of magnitude as those previously reported betweenA. fumigatusstrains. In contrast, similar to what has previously been reported, the two species exhibit high genomic similarity; ∼90% of theA. fumigatusproteome is conserved inA. fischeri, including 48/49 genes known to be involved inA. fumigatusvirulence. However, only 10/33A. fumigatusbiosynthetic gene clusters (BGCs) likely involved in secondary metabolite production are conserved inA. fischeriand only 13/48A. fischeriBGCs are conserved inA. fumigatus. Detailed chemical characterization ofA. fischericultures grown on multiple substrates identified multiple secondary metabolites, including two new compounds and one never before isolated as a natural product. Additionally, anA. fischerideletion mutant oflaeA, a master regulator of secondary metabolism, produced fewer secondary metabolites and in lower quantities, suggesting that regulation of secondary metabolism is at least partially conserved. These results suggest that the nonpathogenicA. fischeripossesses many of the genes important forA. fumigatuspathogenicity but is divergent with respect to its ability to thrive under host-relevant conditions and its secondary metabolism.IMPORTANCEAspergillus fumigatusis the primary cause of aspergillosis, a devastating ensemble of diseases associated with severe morbidity and mortality worldwide.A. fischeriis a close relative ofA. fumigatusbut is not generally observed to cause human disease. To gain insights into the underlying causes of this remarkable difference in pathogenicity, we compared two representative strains (one from each species) for a range of pathogenesis-relevant biological and chemical characteristics. We found that disease progression in multipleA. fischerimouse models was slower and caused less mortality thanA. fumigatus. Remarkably, the observed differences betweenA. fischeriandA. fumigatusstrains examined here closely resembled those previously described for two commonly studiedA. fumigatusstrains, AF293 and CEA10.A. fischeriandA. fumigatusexhibited different growth profiles when placed in a range of stress-inducing conditions encountered during infection, such as low levels of oxygen and the presence of chemicals that induce the production of reactive oxygen species. We also found that the vast majority ofA. fumigatusgenes known to be involved in virulence are conserved inA. fischeri, whereas the two species differ significantly in their secondary metabolic pathways. These similarities and differences that we report here are the first step toward understanding the evolutionary origin of a major fungal pathogen.

scholarly journals Long-read metagenomics of soil communities reveals phylum-specific secondary metabolite dynamics

2021 ◽  
Author(s):  
Marc W. Van Goethem ◽  
Andrew R. Osborn ◽  
Benjamin P. Bowen ◽  
Peter F. Andeer ◽  
Tami L. Swenson ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Temporal Dynamics ◽  
Functional Characterization ◽  
Gene Clusters ◽  
Metagenomic Sequencing ◽  
Pronounced Increase ◽  
Environmental Processes ◽  
Soil Communities ◽  
Functional Dynamics ◽  
Long Read

AbstractMicrobial biosynthetic gene clusters (BGCs) encoding secondary metabolites are thought to impact a plethora of biologically mediated environmental processes, yet their discovery and functional characterization in natural microbiomes remains challenging. Here we describe deep long-read sequencing and assembly of metagenomes from biological soil crusts, a group of soil communities that are rich in BGCs. Taking advantage of the unusually long assemblies produced by this approach, we recovered nearly 3,000 BGCs for analysis, including 695 novel, full-length BGCs. Functional exploration through metatranscriptome analysis of a 3-day wetting experiment uncovered phylum-specific BGC expression upon activation from dormancy, elucidating distinct roles and complex phylogenetic and temporal dynamics in wetting processes. For example, a pronounced increase in BGC transcription occurs at night in cyanobacteria but not in other phyla, implicating BGCs in nutrient scavenging roles and niche competition. Taken together, our results demonstrate that long-read metagenomic sequencing combined with metatranscriptomic analysis provides a direct view into the functional dynamics of BGCs in environmental processes and suggests a central role of secondary metabolites in maintaining phylogenetically conserved niches within biocrusts.

scholarly journals IMG-ABC v.5.0: an update to the IMG/Atlas of Biosynthetic Gene Clusters Knowledgebase

2019 ◽  
Author(s):  
Krishnaveni Palaniappan ◽  
I-Min A Chen ◽  
Ken Chu ◽  
Anna Ratner ◽  
Rekha Seshadri ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Microbial Genomes ◽  
Initial Release ◽  
Systematic Identification ◽  
Biomedical Potential ◽  
Biosynthetic Machinery

Abstract Microbial secondary metabolism is a reservoir of bioactive compounds of immense biotechnological and biomedical potential. The biosynthetic machinery responsible for the production of these secondary metabolites (SMs) (also called natural products) is often encoded by collocated groups of genes called biosynthetic gene clusters (BGCs). High-throughput genome sequencing of both isolates and metagenomic samples combined with the development of specialized computational workflows is enabling systematic identification of BGCs and the discovery of novel SMs. In order to advance exploration of microbial secondary metabolism and its diversity, we developed the largest publicly available database of predicted BGCs combined with experimentally verified BGCs, the Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters (IMG-ABC) (https://img.jgi.doe.gov/abc-public). Here we describe the first major content update of the IMG-ABC knowledgebase, since its initial release in 2015, refreshing the BGC prediction pipeline with the latest version of antiSMASH (v5) as well as presenting the data in the context of underlying environmental metadata sourced from GOLD (https://gold.jgi.doe.gov/). This update has greatly improved the quality and expanded the types of predicted BGCs compared to the previous version.

scholarly journals Variation Among Biosynthetic Gene Clusters, Secondary Metabolite Profiles, and Cards of Virulence Across Aspergillus Species

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 481-497 ◽  
Author(s):  
Jacob L. Steenwyk ◽  
Matthew E. Mead ◽  
Sonja L. Knowles ◽  
Huzefa A. Raja ◽  
Christopher D. Roberts ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Secondary Metabolite ◽  
Immune Cell ◽  
Sequence Divergence ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Host Immune System ◽  
Biosynthetic Gene ◽  
Genetic Determinants

Aspergillus fumigatus is a major human pathogen. In contrast, Aspergillus fischeri and the recently described Aspergillus oerlinghausenensis, the two species most closely related to A. fumigatus, are not known to be pathogenic. Some of the genetic determinants of virulence (or “cards of virulence”) that A. fumigatus possesses are secondary metabolites that impair the host immune system, protect from host immune cell attacks, or acquire key nutrients. To examine whether secondary metabolism-associated cards of virulence vary between these species, we conducted extensive genomic and secondary metabolite profiling analyses of multiple A. fumigatus, one A. oerlinghausenensis, and multiple A. fischeri strains. We identified two cards of virulence (gliotoxin and fumitremorgin) shared by all three species and three cards of virulence (trypacidin, pseurotin, and fumagillin) that are variable. For example, we found that all species and strains examined biosynthesized gliotoxin, which is known to contribute to virulence, consistent with the conservation of the gliotoxin biosynthetic gene cluster (BGC) across genomes. For other secondary metabolites, such as fumitremorgin, a modulator of host biology, we found that all species produced the metabolite but that there was strain heterogeneity in its production within species. Finally, species differed in their biosynthesis of fumagillin and pseurotin, both contributors to host tissue damage during invasive aspergillosis. A. fumigatus biosynthesized fumagillin and pseurotin, while A. oerlinghausenensis biosynthesized fumagillin and A. fischeri biosynthesized neither. These biochemical differences were reflected in sequence divergence of the intertwined fumagillin/pseurotin BGCs across genomes. These results delineate the similarities and differences in secondary metabolism-associated cards of virulence between a major fungal pathogen and its nonpathogenic closest relatives, shedding light onto the genetic and phenotypic changes associated with the evolution of fungal pathogenicity.

scholarly journals Genome, Transcriptome, and Functional Analyses of Penicillium expansum Provide New Insights Into Secondary Metabolism and Pathogenicity

2015 ◽  
Vol 28 (3) ◽  
pp. 232-248 ◽  
Author(s):  
Ana-Rosa Ballester ◽  
Marina Marcet-Houben ◽  
Elena Levin ◽  
Noa Sela ◽  
Cristina Selma-Lázaro ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Plant Pathogens ◽  
Citrus Fruit ◽  
Genomic Analysis ◽  
Pathogenic Fungi ◽  
Gene Clusters ◽  
Penicillium Expansum ◽  
Pome Fruit ◽  
Penicillium Species

The relationship between secondary metabolism and infection in pathogenic fungi has remained largely elusive. The genus Penicillium comprises a group of plant pathogens with varying host specificities and with the ability to produce a wide array of secondary metabolites. The genomes of three Penicillium expansum strains, the main postharvest pathogen of pome fruit, and one Pencillium italicum strain, a postharvest pathogen of citrus fruit, were sequenced and compared with 24 other fungal species. A genomic analysis of gene clusters responsible for the production of secondary metabolites was performed. Putative virulence factors in P. expansum were identified by means of a transcriptomic analysis of apple fruits during the course of infection. Despite a major genome contraction, P. expansum is the Penicillium species with the largest potential for the production of secondary metabolites. Results using knockout mutants clearly demonstrated that neither patulin nor citrinin are required by P. expansum to successfully infect apples. Li et al. ( MPMI-12-14-0398-FI ) reported similar results and conclusions in MPMI's June 2015 issue.

scholarly journals Influence of Niche-Specific Nutrients on Secondary Metabolism in Vibrionaceae

2016 ◽  
Vol 82 (13) ◽  
pp. 4035-4044 ◽  
Author(s):  
Sonia Giubergia ◽  
Christopher Phippen ◽  
Charlotte H. Gotfredsen ◽  
Kristian Fog Nielsen ◽  
Lone Gram
Keyword(s):  
Antibacterial Activity ◽  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Natural Environment ◽  
High Resolution Mass Spectrometry ◽  
Fold Increase ◽  
Gene Clusters ◽  
Growth Potential ◽  
Antibacterial Compounds ◽  
Content Type

ABSTRACTMany factors, such as the substrate and the growth phase, influence biosynthesis of secondary metabolites in microorganisms. Therefore, it is crucial to consider these factors when establishing a bioprospecting strategy. Mimicking the conditions of the natural environment has been suggested as a means of inducing or influencing microbial secondary metabolite production. The purpose of the present study was to determine how the bioactivity ofVibrionaceaewas influenced by carbon sources typical of their natural environment. We determined how mannose and chitin, compared to glucose, influenced the antibacterial activity of a collection ofVibrionaceaestrains isolated because of their ability to produce antibacterial compounds but that in subsequent screenings seemed to have lost this ability. The numbers of bioactive isolates were 2- and 3.5-fold higher when strains were grown on mannose and chitin, respectively, than on glucose. As secondary metabolites are typically produced during late growth, potential producers were also allowed 1 to 2 days of growth before exposure to the pathogen. This strategy led to a 3-fold increase in the number of bioactive strains on glucose and an 8-fold increase on both chitin and mannose. We selected two bioactive strains belonging to species for which antibacterial activity had not previously been identified. Using ultrahigh-performance liquid chromatography–high-resolution mass spectrometry and bioassay-guided fractionation, we found that the siderophore fluvibactin was responsible for the antibacterial activity ofVibrio furnissiiandVibrio fluvialis. These results suggest a role of chitin in the regulation of secondary metabolism in vibrios and demonstrate that considering bacterial ecophysiology during development of screening strategies will facilitate bioprospecting.IMPORTANCEA challenge in microbial natural product discovery is the elicitation of the biosynthetic gene clusters that are silent when microorganisms are grown under standard laboratory conditions. We hypothesized that, since the clusters are not lost during proliferation in the natural niche of the microorganisms, they must, under such conditions, be functional. Here, we demonstrate that an ecology-based approach in which the producer organism is allowed a temporal advantage and where growth conditions are mimicking the natural niche remarkably increases the number ofVibrionaceaestrains producing antibacterial compounds.

scholarly journals Fusarium verticillioides SGE1 Is Required for Full Virulence and Regulates Expression of Protein Effector and Secondary Metabolite Biosynthetic Genes

2014 ◽  
Vol 27 (8) ◽  
pp. 809-823 ◽  
Author(s):  
Daren W. Brown ◽  
Mark Busman ◽  
Robert H. Proctor
Keyword(s):  
Secondary Metabolism ◽  
Fusarium Verticillioides ◽  
Fusaric Acid ◽  
Orthologous Gene ◽  
Gene Clusters ◽  
Effector Proteins ◽  
Surface Proteins ◽  
Regulation Of Transcription ◽  
In Planta ◽  
Food And Feed

The transition from one lifestyle to another in some fungi is initiated by a single orthologous gene, SGE1, that regulates markedly different genes in different fungi. Despite these differences, many of the regulated genes encode effector proteins or proteins involved in the synthesis of secondary metabolites (SM), both of which can contribute to pathogenicity. Fusarium verticillioides is both an endophyte and a pathogen of maize and can grow as a saprophyte on dead plant material. During growth on live maize plants, the fungus can synthesize a number of toxic SM, including fumonisins, fusarins, and fusaric acid, that can contaminate kernels and kernel-based food and feed. In this study, the role of F. verticillioides SGE1 in pathogenicity and secondary metabolism was examined by gene deletion analysis and transcriptomics. SGE1 is not required for vegetative growth or conidiation but is required for wild-type pathogenicity and affects synthesis of multiple SM, including fumonisins and fusarins. Induced expression of SGE1 enhanced or reduced expression of hundreds of genes, including numerous putative effector genes that could contribute to growth in planta; genes encoding cell surface proteins; gene clusters required for synthesis of fusarins, bikaverin, and an unknown metabolite; as well as the gene encoding the fumonisin cluster transcriptional activator. Together, our results indicate that SGE1 has a role in global regulation of transcription in F. verticillioides that impacts but is not absolutely required for secondary metabolism and pathogenicity on maize.

scholarly journals Biosynthetic gene clusters, secondary metabolite profiles, and cards of virulence in the closest nonpathogenic relatives of Aspergillus fumigatus

2020 ◽  
Author(s):  
Jacob L. Steenwyk ◽  
Matthew E. Mead ◽  
Sonja L. Knowles ◽  
Huzefa A. Raja ◽  
Christopher D. Roberts ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Aspergillus Fumigatus ◽  
Secondary Metabolism ◽  
Human Disease ◽  
Metabolic Pathways ◽  
Fungal Pathogen ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Close Relatives

AbstractAspergillus fumigatus is a major human pathogen that causes hundreds of thousands of infections yearly with high mortality rates. In contrast, Aspergillus fischeri and the recently described Aspergillus oerlinghausenensis, the two species most closely related to A. fumigatus, are not known to be pathogenic. Some of the “cards of virulence” that A. fumigatus possesses are secondary metabolites that impair the host immune system, protect from host immune cell attacks, or acquire key nutrients. Secondary metabolites and the biosynthetic gene clusters (BGCs) that typically encode them often vary within and between fungal species. To gain insight into whether secondary metabolism-associated cards of virulence vary between A. fumigatus, A. oerlinghausenensis, and A. fischeri, we conducted extensive genomic and secondary metabolite profiling analyses. By analyzing multiple A. fumigatus, one A. oerlinghausenensis, and multiple A. fischeri strains, we identified both conserved and diverged secondary metabolism-associated cards of virulence. For example, we found that all species and strains examined biosynthesized the major virulence factor gliotoxin, consistent with the conservation of the gliotoxin BGC across genomes. However, species differed in their biosynthesis of fumagillin and pseurotin, both contributors to host tissue damage during invasive aspergillosis; these differences were reflected in sequence divergence of the intertwined fumagillin/pseurotin BGCs across genomes. These results delineate the similarities and differences in secondary metabolism-associated cards of virulence between a major fungal pathogen and its nonpathogenic closest relatives, shedding light into the genetic and phenotypic changes associated with the evolution of fungal pathogenicity.ImportanceThe major fungal pathogen Aspergillus fumigatus kills tens of thousands each year. In contrast, the two closest relatives of A. fumigatus, namely Aspergillus fischeri and Aspergillus oerlinghausenensis, are not considered pathogenic. A. fumigatus virulence stems, partly, from its ability to produce small molecules called secondary metabolites that have potent activities during infection. In this study, we examined whether A. fumigatus secondary metabolites and the metabolic pathways involved in their production are conserved in A. oerlinghausenensis and A. fischeri. We found that the nonpathogenic close relatives of A. fumigatus produce some, but not all, secondary metabolites thought to contribute to the success of A. fumigatus in causing human disease and that these similarities and differences were reflected in the underlying metabolic pathways involved in their biosynthesis. Compared to its nonpathogenic close relatives, A. fumigatus produces a distinct cocktail of secondary metabolites, which likely contributes to these organisms’ vastly different potentials to cause human disease. More broadly, the study of nonpathogenic organisms that have virulence-related traits, but are not currently considered agents of human disease, may facilitate the prediction of species capable of posing future threats to human health.

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