Nigericin is a polyether antibiotic produced by Streptomyces, notably S. hygroscopicus, isolated in the 1950s. Its complex structure was finally elucidated in 1968. Although Nigericin can be isolated as the free acid (under acidic conditions), like most ionophores it is extracted into organic solvents and is most conveniently isolated as a salt. In vitro, nigericin has broad biological activity against Gram-positive bacteria, fungi, tumor cell lines and some viruses, including HIV. Nigericin is the most common member of the polyether class which are common false positives in in vitro screening bioassays using crude microbial extracts. They are thus important standards for dereplication.
Nigericin is soluble in ethanol, methanol, DMF or DMSO. Poor water solubility.
| Mechanism of Action | Nigericin is an ionophore, possessing very high affinity for monovalent cations such as Na+ and K+. Nigericin disrupts membrane potential and Golgi apparatus in mitochondria. |
| Spectrum | Nigericin has broad in vitro biological activity against Gram-positive bacteria, fungi, tumor cell lines, and some viruses including HIV. |
| Microbiology Applications | Nigerin caused concentration-dependent inhibition of HIV type 1 replication in primary infected cultures of human T-lymhoblastoid H9 cells (Nakamura et al, 1992). |
| Eukaryotic Cell Culture Applications |
Nigericin was used to verify whether glucose transport in 3T3-L1 adipocytes was modulated by changes in intracellular pH since it is a K+/H+ exchanger. Results showed that it increased basal but decreased insulin-stimulated glucose uptake in a time and dose-dependent way. Nigericin may inhibit insulin-stimulated glucose transport mainly by interfering wtih GLUT4 translocation (Chu et al, 2002). Nigericin was used to study cholesterol delivery from the outer mitochondrial membrane to the inner mitochondrial membrane via the steroidogenic acute regulatory protein (StAR). The mechanims by which this protein acts is poorly understood. In this study, it was shown for the first time in true steroidogenic cells (MA-10 mouse Leydig tumor cells) that StAR can act prior to being fully imported into the mitochondria. These results support the theory that at DeltaPsi-dependent factor is needed for StAR activity and that Nigericin can inhibit StAR accumulation without affecting steroidogeneis (King et al, 2000). |
| References |
Chu CY, Kao Y and Fong JC et al (2002) Nigericin inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes. J. Cell. Biochem. 85:83-91 PMID 11891852 Harned RL, Hidy PH, Corum CJ and Jones KL (1951) Nigericin, a new crystalline antibiotic from an unidentified streptomyces. Antibiot. Chemother. 1:594-596 PMID 24541690 King SR, Walsh LP and Stocco DM (2000) Nigericin inhibits accumulation of the steroidogenic acute regulatory protein but not steroidogenesis. Mol. Cell. Endocrinol. 166:147-153 PMID 10996433 Nakamura M et al (1992) Inhibitory effects of polyethers on human immunodeficiency virus replication. Antimicrob. Ag. Chemother. 36:492-494 PMID 1605620 Rodriguez R and Sitges M (1996) Nigericin-induced Na+/H+ and K+/H+ exchange in synaptosomes: effect on [3H]GABA release. Neurochem. Res. 21(8):889-895 PMID 8895841 Steinrauf LK, Pinkerton M and Chamberlin JW (1968) The structure of Nigericin. Biochem. Biophys. Res. Commun. 33(1):29-31 PMID 5696503 |
