Adhesins in the virulence of opportunistic fungal pathogens of human

Abstract

Aspergillosis, candidiasis, and cryptococcosis are the most common cause of mycoses-related disease and death among immune-compromised patients. Adhesins are cell-surface exposed proteins or glycoproteins of pathogens that bind to the extracellular matrix (ECM) constituents or mucosal epithelial surfaces of the host cells. The forces of interaction between fungal adhesins and host tissues are accompanied by ligand binding, hydrophobic interactions and protein-protein aggregation. Adherence is the primary and critical step involved in the pathogenesis; however, there is limited information on fungal adhesins compared to that on the bacterial adhesins. Except a few studies based on screening of proteome for adhesin identification, majority are based on characterization of individual adhesins. Recently, based on their characteristic signatures, many putative novel fungal adhesins have been predicted using bioinformatics algorithms. Some of these novel adhesin candidates have been validated by in-vitro studies; though, most of them are yet to be characterised experimentally. Morphotype specific adhesin expression as well as tissue tropism are the crucial determinants for a successful adhesion process. This review presents a comprehensive overview of various studies on fungal adhesins and discusses the targetability of the adhesins and adherence phenomenon, for combating the fungal infection in a preventive or therapeutic mode.

Hypoxic conditions promote Candida glabrata colonization in the intestinal tract and EPA6 plays a significant role in hypoxic adhesion to intestinal cells

“…This study indicates that Epa6p is the most important factor, especially under anaerobic conditions, for C. glabrata adhesion to the intestinal tract. Indeed, adhesion to host tissues or indwelling medical devices is an important first step in establishing fungal infection and is thus a crucial virulence factor [27]. If Epa6p function could be inhibited, it could contribute to reducing endogenous infection and biofilm formation.…”

Cyclic Tetrapeptides with Synergistic Antifungal Activity from the Fungus Aspergillus westerdijkiae Using LC-MS/MS-Based Molecular Networking

“…An estimated 1.2 billion people worldwide suffer from a fungal disease, of which 1.5 to 2 million people die of a fungal infection each year, surpassing those killed by either malaria or tuberculosis [ 40 , 41 , 42 ]. About 30% of serious infections are caused by Candida albicans , with a mortality rate of up to 40% [ 43 ].…”

Comprehensive Review on the Virulence Factors and Therapeutic Strategies with the Aid of Artificial Intelligence against Mucormycosis

“…The most common virulence factors include cell wall adhesins aiding in host cell penetration, factors helping the fungi to compete for resources, and sporeassociated defense mechanisms to thwart innate and adaptive immune mechanisms including ceasing phagosome maturation in macrophages and neutrophils. 144,176,177 Mucorales utilize various strategies to evade host defenses:…”

“…Once spores cross the physical barriers, macrophages and neutrophils are rapidly recruited to the infection site. The most common virulence factors include cell wall adhesins aiding in host cell penetration, factors helping the fungi to compete for resources, and spore-associated defense mechanisms to thwart innate and adaptive immune mechanisms including ceasing phagosome maturation in macrophages and neutrophils. ,, Mucorales utilize various strategies to evade host defenses: Rhizopus species maintain dormancy inside macrophages via iron restriction (Fet3 and Ftr1 upregulation inside phagosome) and phagosome maturation inhibition (via melanin surface retention on fungal spores). , M. circinelloides activates specific transcription factors (Activating Transcription Factors: Atf1 and Atf2) for germination inside phagosomes, which inhibits noncanonical RNAi pathway (NCRIP), overcoming the host defenses ,, Other Mucor species impede phagosome maturation via the calcineurin pathway using CnbR mutants R. microsporus interacts with a bacterial endosymbiont, Ralstonia pickettii to shield spores from macrophage clearance. ,, Mucormycosis-induced apoptosis in macrophages was studied by López-Muñoz et al in a zebrafish model. , Spore size influences M. circinelloides ’ fate post-phagocytosis: larger spores destroy host cells, while smaller ones are retained, preventing germination …”