Novel Epigallocatechin Gallate (EGCG) Analogs with Improved Biochemical Properties for Targeting Extracellular and Intracellular <i>Staphylococcus aureus</i>
<i>Staphylococcus aureus</i> is a leading cause of bloodstream infection (SAB), with up to 30% mortality. Despite treatment with standard antibiotics, one in three patients develops a persistent infection, which portends a five-fold increase in the risk of death. Persistent SAB has been...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Applied Microbiology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-8007/4/4/107 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <i>Staphylococcus aureus</i> is a leading cause of bloodstream infection (SAB), with up to 30% mortality. Despite treatment with standard antibiotics, one in three patients develops a persistent infection, which portends a five-fold increase in the risk of death. Persistent SAB has been attributed in part to the inability of antistaphylococcal antibiotics to eradicate intracellular <i>S. aureus</i> surviving inside macrophages. (-)- Epigallocatechin gallate (EGCG) is a catechin found in green tea that has been widely studied for its broad biological activities, ranging from anticancer to antibacterial activity. However, EGCG is greatly limited by its poor drug-like properties in terms of stability, membrane permeability, and bioavailability. In this study, we established through a series of in vitro experiments that structural modifications of EGCG enhanced drug-like properties while maintaining or improving its antistaphylococcal activity. Our lead EGCG analogs (MCC-1 and MCC-2) showed improved biochemical properties along with increased potency against extracellular <i>S. aureus</i> and restored susceptibility of β-lactam agents to methicillin-resistant <i>S. aureus</i> (MRSA). Importantly, the lead analogs but not EGCG potentiated macrophage- and antibiotic-mediated clearance of intracellular bacteria. Overall, EGCG analogs showed promise for further development as adjunctive therapy candidates for the treatment of SAB. |
|---|---|
| ISSN: | 2673-8007 |