Aspergillus flavus isolates from Fungal Rhinosinusitis are aflatoxigenic and azole resistant

Author:

Dr Sarah Ahmed (NL)

Abstract:

Background:
Fungal rhinosinusitis (FRS) is a global concern, with a particular impact in arid regions. In Sudan, Aspergillus species are frequent causes of FRS, some of which produce mycotoxins, notably the carcinogen aflatoxins. This study aimed to provide comprehensive insights into the prevalence, identification, antifungal susceptibility, and aflatoxin profiles of FRS-causing agents over a five-year period in Sudan.
Methods:
Our study encompassed 549 nasal biopsies collected over 5 years period. Of the positive culture, 94 isolates were chosen for molecular identification using β-tubulin and calmodulin sequencing. Antifungal susceptibility profiles were assessed by EUCAST protocol. Thin-layer (TLC) and high-performance chromatography (HPLC) were employed to evaluate aflatoxin production under varying incubation conditions, and aflatoxin-associated genes were detected as well. Relative expression of aflD and aflR was studied under conditions simulating a human environment.
Results:
The total positive fungi were 284 identified as follows: A. flavus complex (n = 244), A. terreus complex (n = 16), A. fumigatus complex (n = 7), and other fungi (n = 17). Molecular identification of 94 Aspergillus strains revealed A. flavus (n = 88) as the most common. Notably, 2.4-4.5% of A. flavus and one A. fumigatus displayed reduced susceptibility to azoles. Despite several mutations revealed in cyp51A of these isolates, none could be directly linked to azole resistance. Aflatoxin production was detected in 40% (37/93) and 45% (42/93) of A. flavus isolates by TLC and by HPLC, respectively. Incubating at 36 °C reduced aflatoxin-producing isolates to 43% (41/93). Nevertheless, certain isolates exhibited increased production at 36 °C. All aflatoxin-producing genotypes possessed the necessary genes, while 27.4% (14/51) of non-producers lacked aflD, aflR, and aflS. Mutations were observed in aflS and aflR genes across both aflatoxin-producing and non-producing isolates. Relative expression of aflD and aflR peaked on the 4th — 6th days on SDB medium and on the 9th day on RPMI medium incubation.
Conclusions: Aspergillus flavus was the most prevalent species involved in FRS. The dynamic gene expression patterns of aflD and aflR enriched our understanding of aflatoxin production regulation. The high proportion of aflatoxigenic isolates and the resistance detected emphasize the health risks associated with A. flavus infections and the need for monitoring antifungal susceptibility and aflatoxin exposure.

Abstract Number: 42

Conference Year: 2024


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