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Reducing Peptidoglycan Crosslinking by Chemical Modulator Reverts β‐lactam Resistance in Methicillin‐Resistant Staphylococcus aureus.

Authors :
Kim, Ji‐Hoon
Lee, Yunmi
Kim, Inseo
Chang, JuOae
Hong, Subin
Lee, Na Kyung
Shum, David
Baek, Seongeun
Kim, Wooseong
Jang, Soojin
Lee, Wonsik
Source :
Advanced Science. 7/24/2024, Vol. 11 Issue 28, p1-12. 12p.
Publication Year :
2024

Abstract

Small molecule can be utilized to restore the effectiveness of existing major classes of antibiotics against antibiotic‐resistant bacteria. In this study, it is demonstrated that celastrol, a natural compound, can modify the bacterial cell wall and subsequently render bacteria more suceptible to β‐lactam antibiotics. It is shown that celastrol leads to incomplete cell wall crosslinking by modulating levels of c‐di‐AMP, a secondary messenger, in methicillin‐resistant Staphylococcus aureus (MRSA). This mechanism enables celastrol to act as a potentiator, effectively rendering MRSA susceptible to a range of penicillins and cephalosporins. Restoration of in vivo susceptibility of MRSA to methicillin is also demonstrated using a sepsis animal model by co‐administering methicillin along with celastrol at a much lower amount than that of methicillin. The results suggest a novel approach for developing potentiators for major classes of antibiotics by exploring molecules that re‐program metabolic pathways to reverse β‐lactam‐resistant strains to susceptible strains. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
21983844
Volume :
11
Issue :
28
Database :
Academic Search Index
Journal :
Advanced Science
Publication Type :
Academic Journal
Accession number :
178591898
Full Text :
https://doi.org/10.1002/advs.202400858