Protective effect of microbisporicin (NAI-107) against vancomycin resistant Enterococcus faecium infection in a Galleria mellonella model

Abstract

Increasing antimicrobial resistance in Enterococcus faecium necessitates the search for novel treatment agents, such as bacteriocins. In this study, we conducted an in vivo assessment of five bacteriocins, namely Lacticin Z, Lacticin Q, Garvicin KS (ABC), Aureocin A53 and Microbisporicin (NAI-107), against vanB-resistant Enterococcus faecium using a Galleria mellonella model. Our in vitro experiments demonstrated the efficacy of all five bacteriocins against vanB-resistant E. faecium with only NAI-107 demonstrating in vivo efficacy. Notably, NAI-107 exhibited efficacy across a range of tested doses, with the highest efficacy observed at a concentration of 16 µg/mL. Mortality rates in the group treated with 16 µg/mL NAI-107 were lower than those observed in the linezolid-treated group. These findings strongly suggest that NAI-107 holds promise as a potential alternative therapeutic agent for treating infections caused by resistant E. faecium and warrants further investigation.

Keywords: Enterococcus faecium; Galleria mellonella; Lantibiotics; Microbisporicin; NAI-107; VanB.

Figure 1

Overview of the in vivo assay in Galleria mellonella model. (Figure was generated using BioRender).

Figure 2

Efficacy of (a) Aureocin A53 (2, 8, and 16 µg/mL) and Linezolid (10 µg/mL) (b) Garvicin KS ABC (4, 8, and 16 µg/mL) (c) Lacticin Q (4, 8, and 16 µg/mL) and (d) Lacticin Z (2, 4, 8, and 16 µg/mL) treatment on G. mellonella larvae. A Negative control group was injected with 30 µL of PBS, and a positive control group was inoculated with 30 µL of PBS containing 2.7 × 10⁷ CFUs of the E. faecium strain. Both test and control groups consisted of 20 larvae and were incubated for 120 h at 37 °C. Symbols represent mean survival of the G. mellonella. *P < 0.01, **P < 0.001, ***P < 0.0001, ****P < 0.00001.

Figure 3

Effectiveness of Microbisporicin (2, 4, 8 and 16 µg/mL) and Linezolid (10 µg/mL) treatments on G. mellonella larvae. A negative control group was injected with 30 µL of PBS, and a positive control group was inoculated with 30 µL of PBS containing 2.7 × 10⁷ CFUs of the E. faecium strain. Both test and control groups consisted of 20 larvae and were incubated for 120 h at 37 °C. Symbols represent mean survival of the G. mellonella. *P < 0.01, **P < 0.001, ***P < 0.0001, ****P < 0.00001.