Pathogenesis ofAspergillus fumigatusin Invasive Aspergillosis

Abstract

SUMMARY Aspergillus species are globally ubiquitous saprophytes found in a variety of ecological niches. Almost 200 species of aspergilli have been identified, less than 20 of which are known to cause human disease. Among them, Aspergillus fumigatus is the most prevalent and is largely responsible for the increased incidence of invasive aspergillosis (IA) in the immunocompromised patient population. IA is a devastating illness, with mortality rates in some patient groups reaching as high as 90%. Studies identifying and assessing the roles of specific factors of A. fumigatus that contribute to the pathogenesis of IA have traditionally focused on single-gene deletion and mutant characterization. In combination with recent large-scale approaches analyzing global fungal responses to distinct environmental or host conditions, these studies have identified many factors that contribute to the overall pathogenic potential of A. fumigatus. Here, we provide an overview of the significant findings regarding A. fumigatus pathogenesis as it pertains to invasive disease.

The putative flavin carrier family FlcA-C is important forAspergillus fumigatusvirulence

“…1,2,[29][30][31][32][33] Aspergillus fumigatus is an opportunistic fungal pathogen and the most important species causing pulmonary fungal infections. 15,[34][35][36][37][38] Although A. fumigatus is able to cause many clinical forms, the most important is the invasive pulmonary aspergillosis (IPA), that has mortality rates as high as 80% in immunosuppressed patients. 15,[36][37][38] We have used used ChIP-seq (Chromatin Immunoprecipitation DNA sequencing) aiming to identify gene targets regulated by CrzA.…”

Role of microglia in fungal infections of the central nervous system

“…94 After inhalation, dissemination to the CNS occurs through the bloodstream and contiguous spread from the orbits, periorbital regions, middle ear, or paranasal sinuses. 95 Similar to CNS granuloma formation in murine models of cryptococcosis, cerebral aspergillosis granuloma is surrounded by microglia, leukocytes, and necrotic neurons. 96 When stimulated by Aspergillus b-glucans, Dectin-1 leads to the release of TNF-a, IL-1b, IL-6, IL-8, IL-12, and CXCL-1.…”

“…Mycotoxins also inhibit phagocytosis, reduce Reactive Oxygen Species (ROS) production by neutrophils and inhibit T cell responses. 95,102 Secretion of gliotoxin makes the fungal conidia less susceptible to opsonization increasing the fungus propensity to invade the CNS through endothelial cell endocytosis. 90,102 When this mold is cultured in human cerebrospinal fluid (CSF) secretes Alp-1, an alkaline protease that can cleave and inactivate complement proteins.…”

In Vitro Interaction between Alginate Lyase and Amphotericin B against Aspergillus fumigatus Biofilm Determined by Different Methods

“…S imilar to biofilm-forming bacteria or yeasts (1), Aspergillus fumigatus, the most prevalent airborne fungal pathogen (2), is now largely acknowledged to be an organism able to grow and develop as a multicellular community (3), in which the hyphae are cohesively bonded together by a hydrophobic extracellular matrix (ECM) (4), under the aerial and static conditions found by the fungus either in vitro or in vivo (5)(6)(7)(8)(9). This growth phenotype, which complies with the definition of a biofilm (10), may help A. fumigatus to colonize the host substratum and to resist phagocytic and antimicrobial attacks, mimicking the typical Candida albicans or bacterial biofilm (8,11).…”