Work

Macrophage Reporter Cell Assay for Screening Immunopharmacological Activity of Cell Wall-Active Antifungals

Year: 2014

Type: article

Abstract: Antifungal exposure can elicit immunological effects that contribute to activity in vivo, but this activity is rarely screened in vitro in a fashion analogous to MIC testing. We used RAW 264.7 murine macrophages that express a secreted embryonic alkaline phosphatase (SEAP) gene induced by transcriptional activation of NF-κB and activator protein 1 (AP-1) to develop a screen for immunopharmacological activity of cell wall-active antifungal agents. Isolates of Candida albicans and Aspergillus fumigatus that conditionally express genes involved in cell wall synthesis were also tested with the reporter macrophages. We found that growth of fungi in subinhibitory concentrations of glucan synthesis inhibitors (caspofungin and enfumafungin A) or repression of the β-glucan catalytic subunit of glucan synthase, FKS1, increased macrophage NF-κB/AP-1 activation in a dectin-1-dependent manner. This pattern of activation was also transiently observed with repression of chitin synthesis in C. albicans or when yeast cells were incubated in low concentrations of the chitin synthesis inhibitor nikkomycin Z.

Source: Antimicrobial Agents and Chemotherapy

DOI: 10.1128/aac.02408-13

Authors: Russell E. Lewis, Guangling Liao, Katherine Young, Cameron Douglas, Dimitrios P. Kontoyiannis

Institutions: University of Houston, Merck & Co., Inc., Rahway, NJ, USA (United States), The University of Texas MD Anderson Cancer Center

Language: English

Topic: Antifungal resistance and susceptibility

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: Pfizer