Lazarte, A. V. | Search bioRxiv

bioRxiv2025

Mycobiome analysis of electronic cigarettes reveals a reservoir of pathogenic yeasts

Research on the health impacts of e-cigarettes has focused on non-infectious manifestations. Given their enclosed plastic design and temperature fluctuations, we hypothesized that e-cigarettes are colonized by pathogenic microbes, thereby contributing to lung disease in users. Using sequencing and culture techniques of the devices and mouthwash of 25 users, we found only a small subset of mouthpieces to contain bacteria, whereas most were abundantly colonized with fungi that were distinct from the oral mycobiota, including the genera Rhodotorula, Aureobasidium, Cystobasidium, and Meyerozyma. Chronic exposure to the most frequently isolated pathogen, Cystobasidium minutum, resulted in mucus hypersecretion and obstructive lung disease in mice, characteristics of chronic bronchitis. We conclude that e-cigarettes are frequently colonized with fungal organisms capable of causing lung disease.

molecular biology↗

bioRxiv2024

The heme-scavenger, hemopexin, protects against fungal lung injury by mitigating NETosis: an experimental and computational study.

Invasive aspergillosis is characterized by lung hemorrhage and release of extracellular heme, which promotes fungal growth. Heme can also mediate tissue injury directly, and both fungal growth and lung injury may induce hemorrhage. To assimilate these interdependent processes, we hypothesized that, during aspergillosis, heme mediates direct lung injury independent of fungal growth, leading to worse infection outcomes, and the scavenger protein, hemopexin, mitigates these effects. Mice with neutropenic aspergillosis were found to have a time-dependent increase in lung extracellular heme and a corresponding hemopexin induction. Hemopexin deficiency resulted in markedly increased lung injury, fungal growth, and lung hemorrhage. Using a computational model of the interactions of Aspergillus, heme, and the host, we predicted a critical role for heme-mediated generation of neutrophil-extracellular traps in this infection. We tested this prediction using a fungal strain unable to grow at body temperature, and found that extracellular heme and fungal exposure synergize to induce lung injury by promoting NET release, and disruption of NETs was sufficient to attenuate lung injury and fungal burden. These data implicate heme-mediated NETosis in both lung injury and fungal growth during aspergillosis, resulting in a detrimental positive feedback cycle that can be interrupted by scavenging heme or disrupting NETs.

immunology↗