Study reveals how infection load and immunity shape antifungal tolerance and resistance in fungal pathogens
Researchers developed a quantitative model to study how tolerant and resistant subpopulations of the fungal pathogen Candidozyma auris emerge and compete during infection in an invertebrate host. The study examined how infection load, antifungal drug treatment, and innate host immunity interact to shape the evolutionary dynamics of this multidrug-resistant pathogen. The findings offer a predictive framework for understanding antimicrobial resistance in fungal infections, which are a growing component of the global AMR crisis.
A new preprint on bioRxiv presents a quantitative population and evolutionary dynamics model for Candidozyma auris (formerly Candida auris), a multidrug-resistant fungal pathogen, using the invertebrate host Galleria mellonella as an infection system with a functional innate immune system. The study distinguishes between two forms of reduced drug susceptibility: tolerance, in which fungi survive treatment by growing slowly, and classical resistance. The model finds that whether tolerant subpopulations, resistant subpopulations, or both come to dominate an infection depends on the interplay of initial infection load, the antifungal drug regimen applied, and the activity of the host's innate immune response. These three factors together determine the establishment and co-existence dynamics of these subpopulations, suggesting that treatment outcomes are highly context-dependent. The work contributes a formal mathematical framework intended to help predict the emergence and spread of antifungal resistance, addressing a recognized gap in the broader antimicrobial resistance field.
What's missing
As a preprint, this study has not yet undergone peer review, so its methods and conclusions have not been independently validated. The model is built on an invertebrate host system (Galleria mellonella), and it remains an open question how well the dynamics translate to vertebrate or human immune contexts. The study does not appear to address adaptive immunity, which could substantially alter resistance dynamics in mammalian hosts.
What different sources said
- bioRxivCenter
Candidozyma auris utilizes transferrin, but not heme-bound iron for in vivo virulence
Related
Gut Bacteria Enzyme Found to Break Down Heat-Processed Food Compounds, Producing Novel Biogenic Amines
Researchers have discovered that an enzyme in common gut bacteria can degrade N-epsilon-carboxymethyllysine (CML), a compound formed during thermal food processing, producing previously unknown biogenic amines. The enzyme, ornithine decarboxylase SpeC from enterobacteria, acts on CML and related modified lysine derivatives through a low-level 'underground' catalytic activity. This finding suggests a previously unrecognized communication axis between thermally processed dietary compounds and gut microbial physiology, with potential implications for host health.
Full-Length Gene Sequencing Reveals Two Distinct Bacterial Communities in Black-Legged Ticks Expanding Into Canada
Researchers used Oxford Nanopore full-length 16S rRNA gene sequencing to characterize the microbiome of Ixodes scapularis black-legged ticks collected in Nova Scotia, Canada, distinguishing between tick-adapted bacteria and environmentally acquired bacteria. The study comes as I. scapularis — the primary vector of Lyme disease — is rapidly expanding northward into Canada due to climate change. The findings suggest that environmentally derived bacteria in tick microbiomes are not mere contamination, which has implications for how tick microbiome data is collected and interpreted across surveillance studies.
Study Identifies Metabolic Link Between Cell Envelope Stress and Biofilm Formation in Bacteria
Researchers have discovered that the metabolite acetyl-CoA directly inhibits enzymes that degrade the bacterial signaling molecule c-di-GMP, connecting cell envelope biosynthesis stress to biofilm formation in Pseudomonas aeruginosa. The study found that sub-inhibitory concentrations of antibiotics targeting early peptidoglycan biosynthesis — but not other antibiotic classes — elevate c-di-GMP levels by reducing phosphodiesterase activity, with acetyl-CoA competing for the enzyme active site. Because the relevant enzyme domain is broadly conserved across bacterial species, this checkpoint mechanism may be widespread and could have implications for understanding antibiotic-induced biofilm responses.