Molecular Basis of Angicin Activity

Vogel, V.; Rodriguez, A.; Kruszewska-Naczk, B.; Mauerer, S.; Olari, L.-R.; Köhler, J.; Yadav, P.; Apolloni, J.; Read, C.; Walther, P.; Weidinger, G.; Münch, J.; Ständker, L.; Spellerberg, B.

doi:10.64898/2026.06.03.729741

bioRxiv · 10.64898/2026.06.03.729741

Molecular Basis of Angicin Activity

Vogel, V.·Rodriguez, A.·Kruszewska-Naczk, B.·Mauerer, S.·Olari, L.-R.·Köhler, J.·Yadav, P.·Apolloni, J.·Read, C.·Walther, P.·Weidinger, G.·Münch, J.·Ständker, L.·Spellerberg, B.

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Abstract

Angicin is a class IId bacteriocin produced by Streptococcus anginosus with activity against Gram-positive pathogens, including Listeria monocytogenes and vancomycin-resistant Enterococcus faecium. While the mannose phosphotransferase system (Man-PTS) has been identified as a receptor in L. monocytogenes, its role in streptococci and the structural determinants of Angicin activity remain unclear. Here, we demonstrate that the Man-PTS is required for Angicin susceptibility in Streptococcus constellatus. A transposon mutant (manM::ISS1) showed complete resistance to Angicin and impaired mannose utilization. Structure-activity relationship analysis of truncated and modified peptides localized antimicrobial activity to the C-terminal region, although none of the variants matched the activity of the full-length peptide. Angicin induced membrane depolarization and pore formation in target bacteria. Residual activity in Man-PTS-impaired L. monocytogenes suggests an additional receptor-independent effect at higher concentrations. In vivo toxicity analysis using zebrafish embryos showed low toxicity at active concentrations. These findings identify the Man-PTS as a receptor for Angicin in streptococci and define structural features associated with its antimicrobial activity.

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Vogel, V., Rodriguez, A., Kruszewska-Naczk, B., Mauerer, S., Olari, L.-R., Köhler, J., Yadav, P., Apolloni, J., Read, C., Walther, P., Weidinger, G., Münch, J., Ständker, L., Spellerberg, B.. 2026-06-04. Molecular Basis of Angicin Activity. https://doi.org/10.64898/2026.06.03.729741

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