Oligopeptide Targeting Sortase A as Potential Anti-infective Therapy for Staphylococcus aureus

Frontiers in Microbiology
Jianfeng WangXuming Deng

Abstract

Sortase A (SrtA)-catalyzed anchorage of surface proteins in most Gram-positive bacteria is indispensable for their virulence, suggesting that this transpeptidase is a promising target for antivirulence therapy. Here, an oligopeptide, LPRDA, was identified as an effective inhibitor of SrtA via virtual screening based on the LPXTG substrate sequence, and it was found to inhibit SrtA activity in vitro and in vivo (IC50 = 10.61 μM) by competitively occupying the active site of SrtA. Further, the oligopeptide treatment had no anti-Staphylococcus aureus activity, but it provided protection against S. aureus-induced mastitis in a mouse model. These findings indicate that the oligopeptide could be used as an effective anti-infective agent for the treatment of infection caused by S. aureus or other Gram-positive bacteria via the targeting of SrtA.

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Citations

Jan 31, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Junxian WangTiedong Wang
May 24, 2020·Scientific Reports·Jason E GosschalkRobert T Clubb
Mar 31, 2021·Drug Discovery Today·Sitah AlharthiZyta Maria Ziora
Jul 9, 2020·Journal of Medicinal Chemistry·Teng YangCai-Guang Yang
Sep 14, 2021·Journal of Medicinal Chemistry·Rachit SapraV Haridas

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Methods Mentioned

BETA
X-ray
Fluorescence
PCR
Assay
light microscopy
ELISA
fluorescence assay
fluorescence spectroscopy

Software Mentioned

Autodock vina
SPSS
AutoDock

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