Safety evaluation of microbisporicin (NAI-107) using zebrafish (Danio rerio) embryo - a pilot study.

Abstract

NAI-107 has demonstrated in vitro and in vivo efficacy against multi drug resistance (MDR) pathogens. Studies using the Galleria mellonella model found NAI-107 effective against Neisseria gonorrhoeae and vanB-resistant Enterococcus faecium, with no toxicity at concentrations up to 64 µg/mL. This pilot study evaluated NAI-107's safety using transgenic zebrafish embryos (kdrl:eGFP) that were exposed to NAI-107 concentrations of 0, 10, 20, and 30 µM from 5 hours post-fertilization (hpf) to 4 days post-fertilization (dpf). No mortality or significant morphological abnormalities were observed across all treatment groups. At 2 dpf, larvae treated with 20 and 30 µM NAI-107 exhibited a significant increase in heart rate (p < 0.05), although other cardiac parameters remain unaffected. At 4 dpf, larvae displayed no significant growth differences but had increased locomotor activity at 20 and 30 µM NAI-107 groups, indicated by the higher total distance moved and mean velocity (p < 0.05). NAI-107, at concentrations up to 30 µM, did not induce significant toxic effects in zebrafish embryos. The absence of adverse impacts on survival or gross morphology suggests a favorable safety margin. However, the observed increases in heart rate and locomotor activity suggest possible subclinical effects at higher concentrations that warrant further investigation.