Aspergillus flavus is the second most common etiological agent of invasive aspergillosis (IA) after A. fumigatus. However, most literature describes IA in relation to A. fumigatus or together with other Aspergillus species. Certain differences exist in IA caused by A. flavus and A. fumigatus and studies on A. flavus infections are increasing. Hence, we performed a comprehensive updated review on IA due to A. flavus. A. flavus is the cause of a broad spectrum of human diseases predominantly in Asia, the Middle East, and Africa possibly due to its ability to survive better in hot and arid climatic conditions compared to other Aspergillus spp. Worldwide, ~10% of cases of bronchopulmonary aspergillosis are caused by A. flavus. Outbreaks have usually been associated with construction activities as invasive pulmonary aspergillosis in immunocompromised patients and cutaneous, subcutaneous, and mucosal forms in immunocompetent individuals. Multilocus microsatellite typing is well standardized to differentiate A. flavus isolates into different clades. A. flavus is intrinsically resistant to polyenes. In contrast to A. fumigatus, triazole resistance infrequently occurs in A. flavus and is associated with mutations in the cyp51C gene. Overexpression of efflux pumps in non-wildtype strains lacking mutations in the cyp51 gene can also lead to high voriconazole minimum inhibitory concentrations. Voriconazole remains the drug of choice for treatment, and amphotericin B should be avoided. Primary therapy with echinocandins is not the first choice but the combination with voriconazole or as monotherapy may be used when the azoles and amphotericin B are contraindicated.

Coronavirus disease (COVID-19)-associated mucormycosis (CAM) is an emerging threat globally, especially in India. More than 40,000 CAM cases have been reported in India. The emergence of CAM cases in India has been attributed to environmental, host, and iatrogenic factors. Mucorales spore burden has been reported globally; however, their presence is higher in tropical countries such as India, contributing to the emergence of CAM. Before the COVID-19 pandemic, patients with diabetes mellitus, haematological malignancies, solid organ transplants, corticosteroid therapy and neutropenia were more prone to mucormycosis, whereas in COVID-19 patients, virus-induced endothelial dysfunction, hyperglycaemia, and immune dysfunction following corticosteroid use increase the risk of acquiring mucormycosis. The interaction of Mucorales spores with the epithelial cells, followed by endothelial invasion, is a crucial step in the pathogenesis of mucormycosis. Endothelial damage and increased endothelial receptor expression induced by COVID-19 infection may predispose patients to CAM. COVID-19 infection may directly induce hyperglycaemia by damaging beta cells of the pancreas or by corticosteroid therapy, which may contribute to CAM pathogenesis. Iron acquisition from the host, especially in diabetic ketoacidosis (DKA) or deferoxamine therapy, is an important virulence trait of Mucorales. Similarly, the hyperferritinaemia caused by COVID-19 may act as a source of iron for Mucorales growth and invasion. In addition, corticosteroid treatment reduces or abolishes the innate immune functions of phagocytic cells contributing to the pathogenesis of CAM. This review aims to discuss primarily the host and iatrogenic factors shared between COVID-19 and mucormycosis that could explain the emergence of CAM.

The emergence of azole-resistant Aspergillus fumigatus (AR Af ) across the world is an important public health concern. We sought to determine if propiconazole, a demethylase inhibitor (DMI) fungicide, exerted a selective pressure for AR Af in a tomato production environment following multiple exposures to the fungicide. A tomato field trial was established in 2019 and propiconazole was applied weekly until harvest. Soil, leaf, and fruit (when present) samples were collected at baseline and after each propiconazole application. A. fumigatus isolates ( n , 178) were recovered and 173 were tested for susceptibility to itraconazole, posaconazole, voriconazole, and propiconazole in accordance with CLSI M38 guidelines. All the isolates were susceptible to medical triazoles and the propiconazole MIC ranged from 0.25 to 8 mg/L. A linear regression model was fitted that showed no longitudinal increment in the log ₂ -fold azole MIC of the isolates collected after each propiconazole exposure compared to the baseline isolates. AsperGenius real-time multiplex assay ruled out TR34/L98H and TR46/Y121F/T289A cyp 51A resistance markers in these isolates. Sequencing of a subset of isolates ( n , 46) demonstrated widespread presence of F46Y/M172V/E427K and F46Y/M172V/N248T/D255E/E427K cyp 51A mutations previously associated with reduced susceptibility to triazoles. IMPORTANCE: The agricultural use of azole fungicides to control plant diseases has been implicated as a major contributor to ARAf infections in humans. Our study did not reveal imposition of selection pressure for ARAf in a vegetable production system. However, more surveillance studies for ARAf in food crop production and other environments are warranted in understanding this public and One Health issue.

Aspergillus fumigatus is a leading global human fungal pathogen. Triazole antifungal drugs are used in clinical settings, while triazole demethylase inhibitor (DMI) fungicides are widely applied in the environment to combat plant fungal diseases. Environmental exposure to triazole fungicides may drive cross-resistance to clinical triazoles. To address limited data on environmental azole-resistant A fumigatus (ARAF) in the United States, we conducted surveillance across 75 sites in Ohio, including agricultural (57.3%), naturalized (25.3%), urban (16%), and commercial (1.3%) environments. Samples collected comprised air (n = 411), soil (n = 352), and compost (n = 42). Nested polymerase chain reaction of 397 airborne spore samples detected A fumigatus DNA in 62.7%, with 35.5% wild-type, 17.9% tandem repeat (TR), and 9.3% with mixed genotypes. TR genotype distribution did not differ by environment or DMI use. Aspergillus fumigatus was cultured from 18.1% of air samples, with 1.5% positive for ARAF. From soil and compost, A fumigatus was recovered from 41.4% of samples, of which 9.2% were positive for ARAF. Compost yielded higher A fumigatus (83.3%) and ARAF (21.4%) than soil (36.4% and 1.7%, respectively). ARAF prevalence was higher in urban (9.5%) than agricultural (2.8%) or naturalized (1.4%) environments. Generalized linear models suggested that compost and propiconazole exposure were significant predictors of ARAF occurrence. Among 72 ARAF isolates, 50% and 43% carried TR34/L98H and TR46/Y121F/T289A mutations, respectively, suggesting these mutations as key resistance signatures in Ohio environments. These findings identify compost and DMI exposure as a fertile milieu for ARAF development, highlight urban hotspots, and underscore the need for One Health approaches to resistance management.