Biology subjects

Melie, T.

Publications and source records attributed to Melie, T..

3 recordsLinked to original sources

bioRxiv2023

Reassessing the origins of pathogenicity in Candida auris and relatives through phylogenomic analysis

Emerging fungal pathogens commonly originate from benign or non-pathogenic strains living in the natural environment. Assessing the evolutionary relationships between pathogenic and non-pathogenic species is one approach for tracing the origins of pathogenicity across species. The recently emerged human pathogen, Candida auris belongs to the Candida/Clavispora clade, a diverse group of 45 yeast species including human pathogens and environmental saprobes. C. auris is believed to have originated in the environment and recently transitioned to a human pathogen. We present a phylogenomic analysis of this clade aimed at testing for patterns implicated in the emergence of pathogenicity using an expanded sample of non-pathogenic strains and species. To build a robust framework for investigating these relationships, we developed a whole-genome sequence dataset of 108 isolates representing 18 species, including 4 newly sequenced species and 18 environmentally isolated strains. Our phylogeny, based on 619 orthologous genes, shows environmentally isolated species and strains interspersed with clinically isolated counterparts, rejecting the hypothesis of a single origin of pathogenicity within the lineage containing C. auris and its closest relatives. Our findings highlight the breadth of environments these yeasts inhabit, and imply, concerningly, that known pathogens could just as easily live outside the human body in diverse natural environments. Based on this result, we suggest that surveillance aimed at detecting emerging pathogens should expand to related environmentally-derived fungi with pathogenic potential. AUTHOR SUMMARYThe rapid rise in the number of fungal pathogens over the past few decades has been linked to climate change, globalization, intensive farming practices, and an increase in immunocompromised individuals. Candida auris is an example of a recently emerged fungal pathogen capable of causing severe disease and large outbreaks in vulnerable patient populations. The evolutionary origins of C. auris are poorly understood, however, they are essential to understanding how and when this pathogen emerged. In this study, we investigated relationships between a sample of pathogenic and non-pathogenic strains and species in the Candida/Clavispora clade, a group of 45 yeast species including human pathogens (including C. auris) and environmental saprobes. We used these relationships to test for patterns that might support differing pathogen emergence hypotheses. We found that the relationships between pathogens and non-pathogens suggest many transitions between humans and other environments, rather than a single origin of pathogenicity. It seems plausible that these pathogens, often found in harsh environmental conditions such as seawater, already possessed traits that make them suitable human pathogens, which are perpetuated by increased at-risk patient populations. We should, therefore, be vigilant in our surveillance for clinical isolation of yeasts belonging to this clade from humans.

evolutionary biology↗

bioRxiv2022

A metagenomic investigation of spatial and temporal changes in sewage microbiomes across a university campus

Wastewater microbial communities are not static and can vary significantly across time and space, but this variation and the factors driving the observed spatiotemporal variation often remain undetermined. We used a shotgun metagenomic approach to investigate changes in wastewater microbial communities across 17 locations in a sewer network, with samples collected from each location over a 3-week period. Fecal-derived bacteria constituted a relatively small fraction of the taxa found in the collected samples, highlighting the importance of environmental sources to the sewage microbiome. The prokaryotic communities were highly variable in composition depending on the location within the sampling network and this spatial variation was most strongly associated with location-specific differences in sewage pH. However, we also observed substantial temporal variation in the composition of the prokaryotic communities at individual locations. This temporal variation was asynchronous across sampling locations, emphasizing the importance of independently considering both spatial and temporal variation when assessing the wastewater microbiome. The spatiotemporal patterns in viral community composition closely tracked those of the prokaryotic communities, allowing us to putatively identify the bacterial hosts of some of the dominant viruses in these systems. Finally, we found that antibiotic resistance gene profiles also exhibit a high degree of spatiotemporal variability with most of these genes unlikely to be derived from fecal bacteria. Together these results emphasize the dynamic nature of the wastewater microbiome, the challenges associated with studying these systems, and the utility of metagenomic approaches for building a multi-faceted understanding of these microbial communities and their functional attributes. ImportanceSewage systems harbor extensive microbial diversity, including microbes derived from both human and environmental sources. Studies of the sewage microbiome are useful for monitoring public health and the health of our infrastructure, but the sewage microbiome can be highly variable in ways that are often unresolved. We sequenced DNA recovered from wastewater samples collected over a 3-week period at 17 locations in a single sewer system to determine how these communities vary across time and space. Most of the wastewater bacteria, and the antibiotic resistance genes they harbor, were not derived from human feces, but human usage patterns did impact how the amounts and types of bacteria and bacterial genes we found in these systems varied over time. Likewise, the wastewater communities, including both bacteria and their viruses, varied depending on location within the sewage network, highlighting the challenges, and opportunities, in efforts to monitor and understand the sewage microbiome.

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↗