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LaeA-dependent production of small molecules of Aspergillus niger that compete with specific antibodies that bind to human immune receptors

Escobar, N.; Keizer, E.; van Neer, J.; Arentshorst, M.; van Strijp, J.; Haas, P.-J.; Ram, A.; Punt, P.; Wosten, H.; de Cock, H.

2022-04-26 microbiology
10.1101/2022.04.26.489527 bioRxiv
Show abstract

Microorganisms secrete a variety of compounds into their environment such as proteins, carbohydrates, and secondary metabolites. These molecules play diverse roles in the interaction of microbes with their abiotic and biotic environment. Little is known about secreted fungal molecules mediating immune evasion. Here we screened culture media of three Aspergilli to assess whether these fungi secrete molecules that can compete with specific antibodies that bind to human immune receptors. Culture media of Aspergillus fumigatus Af293, Aspergillus tubingensis CBS 133792 and the non-acidifying mutant strain Aspergillus niger D15#26 contained components that showed competition for binding to a total of 13 receptors, of which PSGL-1, CXCR1, and CXCR2, were shared between the three species. Filtration experiments showed that most, if not all, interacting components were [≤] 3 kDa. Production of the components that competed with antibodies to bind to CD88 and CXCR2 was shown to be regulated by LaeA. The component(s) that competed for binding to CXCR1 was not only produced in the non-acidifying strain Aspergillus niger D15#26 but also in the non-acidifying oahA deletion strain of Aspergillus niger. Together, these data show that Aspergillus species might produce small molecules that interact with human immune receptors.

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