Biology subjects

Mangum, B.

Publications and source records attributed to Mangum, B..

4 recordsLinked to original sources

bioRxiv2025

Pan-genome analyses of 226 finger millet-infecting Magnaporthe oryzae strains from eastern Africa reveal two lineages that differ in their genetic make-up, virulence and effector gene content with gene loss driven by homologous recombination between Pot2 elements

Blast disease, caused by the filamentous ascomycete Magnaporthe oryzae, is the main biotic constraint to finger millet production in eastern Africa. M. oryzae is a pathogen on many grass species, but the high host-specificity of blast isolates underscores the need to study pathogen diversity and virulence at the host level. Here, we fill a void on knowledge on finger millet-infecting strains of M. oryzae by sequencing 226 isolates pure-cultured from infected tissues, mainly peduncles and panicles, sampled from field-grown finger millet accessions across Ethiopia, Kenya, Tanzania and Uganda. Phylogenetic analysis showed that eastern African isolates are genetically distinct from Asian isolates, and differentiated into two groups potentially driven by climate variables. One group was dominated by isolates from Kenya and Uganda (KU group), and the other by isolates from Ethiopia and Tanzania (ET group). Analysis of the portfolio of 887 predicted effector genes showed that the KU group had significantly fewer effectors, concomitant with higher virulence levels on the two finger millet accessions tested. We demonstrate that homologous recombination between transposable elements, leading to genomic deletions, plays a key role in gene removal. Transcript profiling of fungal genes in compatible and incompatible interactions revealed upregulation in the incompatible interaction as a characteristic of an estimated 30% of effector genes, including seven of the eight homologs of known avirulence genes from rice-infecting M. oryzae identified in our study. Prioritization of these effectors for functional validation will pave the way for identifying cognate resistance genes and improving finger millet for resistance to blast disease.

plant 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↗

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↗