Special Issue: Frontiers in Antimicrobial Drug Discovery and Design

Barlocco, Daniela; Meneghetti, Fiorella

doi:10.3390/molecules22071127

Cited by 2 publications

(1 citation statement)

References 13 publications

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“…SrtA mediates the secretion of these adhesions by S. aureus . Therefore, SrtA is considered an ideal target for designing new anti-infective agents, disturbing bacterial virulence, but it will not interfere with bacterial vitality like antibiotics [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Cyanidin chloride protects mice from methicillin-resistant Staphylococcus aureus-induced pneumonia by targeting Sortase A

Wang

et al. 2022

Virulence

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Methicillin-resistant Staphylococcus aureus (MRSA) has been developing rapidly in recent years. It poses a severe peril to global health care, and the new strategies to against the MRSA is urgently needed. Sortase A (SrtA) regulates the anchoring of many surface proteins. Compounds repress Staphylococcus aureus ( S. aureus ) cysteine transpeptidase SrtA are considered adequate potent virulence inhibitors. Then, we describe the identification of an effective SrtA inhibitor, cyanidin chloride, a bioflavonoid compound isolated from various plants. It has a reversible inhibitory effect on SrtA activity at an IC 50 of 21.91 μg/mL. As a SrtA inhibitor, cyanidin chloride antagonizes SrtA-related virulence phenotypes due to its breadth and specificity, including fibrinogen adhesion, A549 cell invasion, biofilm formation, and surface protein (SpA) anchoring. Subsequently, molecular docking and fluorescence quenching revealed that SrtA and cyanidin chloride had robust mutual affinity. Further mechanistic studies revealed that Arg-197, Gly-167, and Sep-116 were the key-binding sites mediating the interaction between SrtA and cyanidin chloride. Notably, a significant therapeutic effect of cyanidin chloride in vivo was also observed on the mouse pneumonia model induced by MRSA. In conclusion, our study indicates that cyanidin chloride potentially represents a new candidate SrtA inhibitor for S. aureus and potentially be developed as a new antivirulence agent.

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Section: Discussionmentioning

confidence: 99%