In a recent study published in the journal Dr PLoS PathogensResearchers discuss cryptic fungal pathogens, which are genetically distinct from pathogens but morphologically indistinguishable.
Fungal pathogens threaten health and food security worldwide. Diagnosis and treatment of fungal infections are complex, leading to serious morbidity and mortality. In addition, cryptic fungal species can also cause infections and are challenging to identify by conventional methods due to morphological similarities. As such, the clinical burden and epidemiology of occult fungi are poorly understood. The present study summarizes the available information on cryptic fungi.
Study: Know the Enemy and Know Thyself: Addressing Enigmatic Fungal Pathogens in Humans and Beyond. Image credit: Created with assistance from DALL·E 3
Diagnosis of fungal pathogens
Accurate diagnosis is essential to reduce the burden of fungal infections. Conventional diagnostic methods include microscopy, histopathology, culture, and matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry. These methods have poor specificity, especially for cryptic species. Nevertheless, molecular typing (phylogenetic analysis) has become more accurate.
However, some loci may not have sufficient information for accurate identification. Aspergillus latus A cryptic species and allodiploid hybrid that has not been detected in clinical settings due to limitations of single-locus typing in a hybrid genome. Comprehensive phenotyping and genome sequencing have provided robust identification A. Lattes. Other approaches, such as phylogenomics, can overcome these limitations.
Although phylogenomics provides high specificity, it requires more time, resources and expertise. Rapid and cost-effective diagnosis is critical to reducing mortality. Note that average nucleotide identity is an unexplored alternative. Comparative analysis of different diagnostic methods will determine the most effective method.
Exemplary known and cryptic pathogenic species of Aspergillus. (Left) Aspergillus fumigatus is a well-known and major human fungal pathogen. The cryptic species (middle) Aspergillus lentulus and (right) Aspergillus udagawai can cause human disease, but A. fumigatus can be difficult to diagnose due to their morphological similarity. Pictures please Dr. Jose Houbracken. https://doi.org/10.1371/journal.ppat.1011704.g001
Humans may unwittingly contribute to the transmission of fungal diseases. For example, outbreaks of invasive fungi have been linked to spread through hospital construction, poor air filtration and contaminated surfaces. In addition, dietary effects on the abundance of specific fungi in the human mycobiome, human-to-human transmission, and fungal immunity may also influence fungal disease.
Examining patient populations and their genetic background will be important to understand how host biology contributes to susceptibility. That is, patients with chronic granulomatous disease are at higher risk of infection A. Nidulans. Notably, associations between cryptic fungal pathogens and specific patient populations are unclear due to a lack of specific diagnoses.
Immune response and disease management
Understanding the interaction of fungal pathogens with the host immune system will provide important insights into their persistence and clearance mechanisms. Some studies have identified immunological checkpoints for pathogen detection. Furthermore, there is considerable variation in the formation of neutrophil extracellular traps, i.e., NETs, across Aspergillus species and strains
In addition, certain congenital abnormalities in immune function may increase susceptibility to infection in certain populations. For example, individuals with chronic granulomatous disease exhibit a high susceptibility to aspergillosis because they have a reduced ability to produce reactive oxygen species (ROS).
Impact of the microbiome and potential future threats
Exploring the human microbiome can help delineate the effects of species on cross-species interactions that may prevent or contribute to disease. Changes in the mycobiome may contribute to disease severity. Pathogens also affect the mycobiome; That is, lung colonization by A. fumigatus The resulting microbiome composition is more favorable for fungal growth.
Although studies on the mycobiome have provided important insights at the genus level, assessing variations at the species or strain level would deepen understanding of how they affect human health and the mycobiome. Cryptic pathogens often go undetected, as detection is only possible at the genus level.
Therefore, species or strain level identification is fundamental due to phenotypic and genotypic variation. Analysis of non-pathogenic species is also essential, as previously unknown species may emerge as pathogens. Exploration of pathogens and related non-pathogenic species can provide insight into the emergence of pathogenicity and evolutionary dynamics.
Addressing these challenges requires establishing the necessary infrastructure for accurate diagnosis and dissemination of results. This will facilitate epidemiology, disease surveillance, and identification of susceptible populations, early outbreaks, and emerging pathogens. Insights from surveillance systems, such as NextStrain and MicroAct, can serve as an inspiration for establishing a fungus-specific platform. Overall, integrating microbiome, pathogen, host genetics and health record data will provide a comprehensive dataset to address the concerns of fungal pathogens.