Accelerating the understanding of Aspergillus terreus: Epidemiology, physiology, immunology and advances

Abstract

Aspergillus species encompass a variety of infections, ranging from invasive aspergillosis to allergic conditions, contingent upon the immune status of the host. In this spectrum, Aspergillus terreus stands out due to its emergence as a notable pathogen and its intrinsic resistance to amphotericin-B. The significance of Aspergillus-associated infections has witnessed a marked increase in the past few decades, particularly with the increasing number of immunocompromised individuals. The exploration of epidemiology, morphological transitions, immunopathology, and novel treatment approaches such as new antifungal drugs (PC945, olorofim) and combinational therapy using antifungal drugs and phytochemicals (Phytochemicals: quercetin, shikonin, artemisinin), also using immunotherapies to modulate immune response has resulted in better outcomes. Furthermore, in the context COVID-19 era and its aftermath, fungal infections have emerged as a substantial challenge for both immunocompromised and immunocompetent individuals. This is attributed to the use of immune-suppressing therapies during COVID-19 infections and the increase in transplant cases. Consequently, this review aims to provide an updated overview encompassing the epidemiology, germination events, immunopathology, and novel drug treatment strategies against Aspergillus terreus-associated infections.

Keywords: Antifungal phytochemicals; Aspergilli; Aspergillus terreus; Cytokines; Echinocandins (PC945, PC1244); Epidemiology; Germination; Immune response; PAMPs; PRRs.

Graphical abstract

Fig. 1

Different developmental stages of Aspergillus terreus and underlying events. Different proteins expressed during different stages of Aspergillus terreus development have been shown (Thakur and Shankar 2017; Thakur and Shankar 2019; Tiwari et al., 2016; Shishodia and Shankar 2020).

Fig. 2

Represents the different features of biofilm formation in Aspergillus terreus. Scanning Electronic Microscopy (SEM) images of biofilm formation in Aspergillus terreus at 48h (inoculums concentration 1 × 10⁶ conidia/mL,) (A) mycelium networks embedded in ECM (Extracellular Matrix), 1000X (B) Hyphae covered with ECM showing superficial appearance, 5000 × (C). Aspergillus terreus biofilm showing porous ECM, 5000 ×.

Fig. 3

Depicting the key determinants contributing to morphological changes as well as factors contributing drug resistance in Aspergillus terreus. (Shishodia et al. 2019; Louis et al., 2014; Thakur and Shankar 2017; Thakur and Shankar 2019; Shishodia and Shankar 2020; Lass-Flörl et al., 2021) 3A. Various Key factors and virulence factors during Germination and hyphae/mycelium formation in Aspergillus terreus, along with the innate/adaptive responses in host cell are summarized. 3B. Key modulators in drug resistance mechanism in Aspergillus terreus are summarized.