Eriodictyol as a Potential Candidate Inhibitor of Sortase A Protects Mice From Methicillin-Resistant Staphylococcus aureus -Induced Pneumonia
New anti-infective approaches are urgently needed to control multidrug-resistant (MDR) pathogens, such as methicillin-resistant (MRSA). Sortase A (SrtA) is a membrane-bound cysteine transpeptidase that plays an essential role in the catalysis of covalent anchoring of surface proteins to the cell wal...
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Published in | Frontiers in microbiology Vol. 12; p. 635710 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
18.02.2021
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Subjects | |
Online Access | Get full text |
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Summary: | New anti-infective approaches are urgently needed to control multidrug-resistant (MDR) pathogens, such as methicillin-resistant
(MRSA). Sortase A (SrtA) is a membrane-bound cysteine transpeptidase that plays an essential role in the catalysis of covalent anchoring of surface proteins to the cell wall of
(
). The present study reports identification of a flavonoid, eriodictyol, as a reversible inhibitor of SrtA with an IC
of 2.229 ± 0.014 μg/mL that can be used as an innovative means to counter both resistance and virulence. The data indicated that eriodictyol inhibited the adhesion of the bacteria to fibrinogen and reduced the formation of biofilms and anchoring of staphylococcal protein A (SpA) on the cell wall. The results of fluorescence quenching experiments demonstrated a strong interaction between eriodictyol and SrtA. Subsequent mechanistic studies revealed that eriodictyol binds to SrtA by interacting with R197 amino acid residue. Importantly, eriodictyol reduced the adhesion-dependent invasion of A549 cells by
and showed a good therapeutic effect in a model of mouse pneumonia induced by
. Overall, the results indicated that eriodictyol can attenuate MRSA virulence and prevent the development of resistance by inhibiting SrtA, suggesting that eriodictyol may be a promising lead compound for the control of MRSA infections. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Guillermo Martín Gutiérrez, Virgen del Rocío University Hospital, Spain; Maria José Saavedra, Universidade de Trás os Montes e Alto Douro, Portugal These authors have contributed equally to this work Edited by: Younes Smani, Institute of Biomedicine of Seville (IBIS), Spain This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology |
ISSN: | 1664-302X 1664-302X |
DOI: | 10.3389/fmicb.2021.635710 |