Aspergillus fumigatus escape mechanisms from its harsh survival environments.

Aspergillus fumigatus is a ubiquitous pathogenic mold and causes several diseases, including mycotoxicosis, allergic reactions, and systemic diseases (invasive aspergillosis), with high mortality rates. In its ecological niche, the fungus has evolved and mastered many reply strategies to resist and survive against negative threats, including harsh environmental stress and deficiency of essential nutrients from natural environments, immunity responses and drug treatments in host, and competition from symbiotic microorganisms. Hence, treating A. fumigatus infection is a growing challenge. In this review, we summarized A. fumigatus reply strategies and escape mechanisms and clarified the main competitive or symbiotic relationships between A. fumigatus, viruses, bacteria, or fungi in host microecology. Additionally, we discussed the contemporary drug repertoire used to treat A. fumigatus and the latest evidence of potential resistance mechanisms. This review provides valuable knowledge which will stimulate further investigations and clinical applications for treating and preventing A. fumigatus infections. KEY POINTS: • Harsh living environment was a great challenge for A. fumigatus survival. • A. fumigatus has evolved multiple strategies to escape host immune responses. • A. fumigatus withstands antifungal drugs via intrinsic escape mechanisms.

The potential role of plant secondary metabolites on antifungal and immunomodulatory effect.

With the widespread use of antibiotic drugs worldwide and the global increase in the number of immunodeficient patients, fungal infections have become a serious threat to global public health security. Moreover, the evolution of fungal resistance to existing antifungal drugs is on the rise. To address these issues, the development of new antifungal drugs or fungal inhibitors needs to be targeted urgently. Plant secondary metabolites are characterized by a wide variety of chemical structures, low price, high availability, high antimicrobial activity, and few side effects. Therefore, plant secondary metabolites may be important resources for the identification and development of novel antifungal drugs. However, there are few studies to summarize those contents. In this review, the antifungal modes of action of plant secondary metabolites toward different types of fungi and fungal infections are covered, as well as highlighting immunomodulatory effects on the human body. This review of the literature should lay the foundation for research into new antifungal drugs and the discovery of new targets. KEY POINTS: • Immunocompromised patients who are infected the drug-resistant fungi are increasing. • Plant secondary metabolites toward various fungal targets are covered. • Plant secondary metabolites with immunomodulatory effect are verified in vivo.

Pathogenesis, Diagnosis, and Treatment of Infectious Rhinosinusitis.

Rhinosinusitis is a common inflammatory disease of the sinonasal mucosa and paranasal sinuses. The pathogenesis of rhinosinusitis involves a variety of factors, including genetics, nasal microbiota status, infection, and environmental influences. Pathogenic microorganisms, including viruses, bacteria, and fungi, have been proven to target the cilia and/or epithelial cells of ciliated airways, which results in the impairment of mucociliary clearance, leading to epithelial cell apoptosis and the loss of epithelial barrier integrity and immune dysregulation, thereby facilitating infection. However, the mechanisms employed by pathogenic microorganisms in rhinosinusitis remain unclear. Therefore, this review describes the types of common pathogenic microorganisms that cause rhinosinusitis, including human rhinovirus, respiratory syncytial virus, Staphylococcus aureus, Pseudomonas aeruginosa, Aspergillus species, etc. The damage of mucosal cilium clearance and epithelial barrier caused by surface proteins or secreted virulence factors are summarized in detail. In addition, the specific inflammatory response, mainly Type 1 immune responses (Th1) and Type 2 immune responses (Th2), induced by the entry of pathogens into the body is discussed. The conventional treatment of infectious sinusitis and emerging treatment methods including nanotechnology are also discussed in order to improve the current understanding of the types of microorganisms that cause rhinosinusitis and to help effectively select surgical and/or therapeutic interventions for precise and personalized treatment.