Biology subjects

Adamu Bukari, A.-R.

Publications and source records attributed to Adamu Bukari, A.-R..

3 recordsLinked to original sources

bioRxiv2026

Global whole-genome phylogenomics of Nakaseomyces glabratus reveals admixture and refines sequence type-based classification

Nakaseomyces glabratus is a globally distributed opportunistic fungal pathogen. An ongoing discussion in studies of N. glabratus population structure has been whether genetic clusters are best defined using multilocus sequence typing (MLST) or short-read whole-genome sequencing (WGS). To assess the concordance between MLST- and WGS-based phylogenies, we analyzed a dataset of 548 N. glabratus WGS sequences from 12 countries. Clusters identified from WGS largely recapitulated the MLST-defined sequence type (ST) groups: fourteen WGS clusters were composed of a single MLST ST, and the remaining contained STs with very closely related MLST profiles. We thus propose a pragmatic naming convention, consistent with the system used in other microbial species, which specifies WGS cluster labels based on the primary ST. From the large WGS isolate dataset, we determined the prevalence of admixture and genomic variants. Interestingly, seven of the nine singleton isolates were admixed, in addition to 58 isolates from six different clusters. Aneuploidy was detected in 4% of isolates, most commonly in chrE, which contains ERG11, the gene encoding the enzyme targeted by azole antifungals. Aneuploid chromosomes did not exhibit elevated heterozygosity relative to the sequencing error rate, consistent with instability of extra chromosome copies. Copy number variants were found in 3% of the isolates; some of the CNVs co-occurred with aneuploidies, and were primarily identified on chrD, chrE, chrI, and chrM. Our findings demonstrate that deep splits between clusters preserve the utility of MLST ST designations for clade-level designation, yet underscore the utility of WGS for high-resolution genomic analyses. Article SummaryThere is an ongoing debate in studies on Nakaseomyces glabratus about whether traditional MLST analysis is sufficient to determine population structure, or whether the precision of whole genome sequencing (WGS) is necessary. We analyzed WGS data from 548 isolates from around the world. We found a very strong agreement between the two methods. We propose a hybrid naming system, where cluster names are based on the dominant MLST group. We used the WGS data to show that admixed isolates, and those with extra chromosomes or CNVs are rare (<7% of isolates in each class) and are distributed throughout the phylogeny.

evolutionary biology↗

bioRxiv2025

Pooled CRISPRi screening reveals fungal-specific vulnerabilities across environments and genetic backgrounds

The rising rate of drug-resistant fungal infections and the emergence of fungal pathogens with intrinsic resistance phenotypes are a growing concern. The close evolutionary distance between mammals and fungi complicates the design of new antifungals and increases the chances of toxic off-target effects. As such, antifungal drug development usually focuses on fungal-specific proteins when considering potential new targets. Ideal drug targets should mediate essential cell processes and be highly sensitive to inhibition. Targeted gene repression can serve as a model for drug-mediated inhibition and for determining the dosage-sensitivity profile of genes of interest. In the fungal pathogen Candida albicans, classical approaches for gene repression can be labour-intensive and limited to one genetic background due to low throughput. Here, we adapt pooled CRISPRi screening in C. albicans for the first time and exploit this technique for large-scale functional genomic analysis. Through pooled CRISPRi screening, we test the repression sensitivity of over a hundred essential genes conserved in fungi but absent in humans, and successfully identify highly dosage-sensitive genes across multiple cell components and pathways. By extending our analysis to ten diverse environmental conditions, we show how the environment influences dosage-sensitivity profiles. Finally, we extend our experiments to two clinical drug-resistant C. albicans strain backgrounds and demonstrate that many of the fitness defects we observed are conserved in resistant clinical isolates. Together, our results highlight a set of genes that are highly dosage-sensitive across different genetic and environmental contexts, making them attractive targets for further investigation. By facilitating rapid, efficient large-scale functional genomics assays across diverse genetic backgrounds, CRISPRi pooled screening will open new frontiers in C. albicans biology.

microbiology↗

bioRxiv2023

Genotypic and phenotypic homogeneity of vaginal and rectal yeast isolates from recurrent vulvovaginal candidiasis

Vulvovaginal candidiasis is one of the most common fungal infections. Most are successfully treated with antifungal drugs, yet [~]8% lead to recurrent vulvovaginal candidiasis ("RVVC"). Previous research found closely-related isolates within vaginal and rectal populations. However, their methods preclude assessing fine-scale relationships among closely related isolates and measuring genetic variation, a fundamental property with evolutionary potential implications. To address this gap, we isolated 12 vaginal and 12 rectal yeast isolates during symptomatic relapse from four individuals with a history of RVVC. Three had Candida albicans infections, while the fourth had Nakaseomyces glabratus. All isolates were whole-genome sequenced and phenotyped. The isolates were placed into global phylogenies built from short-read WGS data, including an updated N. glabratus tree with over 500 isolates. Genotypic and phenotypic analyses were consistent with migration between sites. There was little phenotypic diversity for drug response and no consistent difference between isolates from different sites for invasive growth. Although there are few comparables, C. albicans nucleotide diversity was similar to most commensal oral and rectal populations, while N. glabratus was similar to some bloodstream infections (though higher than others). Single nucleotide changes drove diversity; no aneuploidies were found, and only a single loss-of-heterozygosity tract on chr1L varied among isolates from one participant. This study provides baseline measurements and describes techniques to quantify within-population diversity in fungal microbes. We highlight a need for comparable studies that use the same sampling effort and analysis methods to understand the interplay in shaping fungal microbial communities in important contexts. Author SummaryRecurrent vaginal yeast infections are relatively common, and we do not understand why some people experience these chronic infections when many others have a single infection that is successfully treated and cleared. Many open questions remain about the basic biology of the yeast populations involved. We quantified diversity using modern sequencing technology within vaginal and rectal yeast populations from four individuals with a history of recurrent yeast infections experiencing symptoms. Three participants had a Candida albicans infection (the most common causative species), while the fourth had a Nakaseomyces glabratus infection (the second most common and increasingly implicated). We found that vaginal and rectal isolates were closely related, indicating the same population is present at the two sites. Surprisingly, we found that diversity was similar to the yeast populations found at other body sites in healthy people. Our study highlights a critical need for additional studies following the same methods in different contexts to better understand the fungal microbial populations in our bodies.

microbiology↗