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...
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MDPI AG
2024-11-01
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| Series: | Applied Microbiology |
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| Online Access: | https://www.mdpi.com/2673-8007/4/4/107 |
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| author | Riley Grosso Vy Nguyen Syed Kaleem Ahmed Annie Wong-Beringer |
| author_facet | Riley Grosso Vy Nguyen Syed Kaleem Ahmed Annie Wong-Beringer |
| author_sort | Riley Grosso |
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| description | <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. |
| format | Article |
| id | doaj-art-7e7eb315655b4cb3bd0ceebb8a8a6f49 |
| institution | Kabale University |
| issn | 2673-8007 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Microbiology |
| spelling | doaj-art-7e7eb315655b4cb3bd0ceebb8a8a6f492024-12-27T14:07:17ZengMDPI AGApplied Microbiology2673-80072024-11-01441568158110.3390/applmicrobiol4040107Novel Epigallocatechin Gallate (EGCG) Analogs with Improved Biochemical Properties for Targeting Extracellular and Intracellular <i>Staphylococcus aureus</i>Riley Grosso0Vy Nguyen1Syed Kaleem Ahmed2Annie Wong-Beringer3Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern Los Angeles, Los Angeles, CA 90033, USAAlfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern Los Angeles, Los Angeles, CA 90033, USAAlfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern Los Angeles, Los Angeles, CA 90033, USAAlfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern Los Angeles, Los Angeles, CA 90033, USA<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.https://www.mdpi.com/2673-8007/4/4/107antibiotic resistanceantibiotic actionchemical modificationdrug designGram-positive bacteriahost–pathogen interaction |
| spellingShingle | Riley Grosso Vy Nguyen Syed Kaleem Ahmed Annie Wong-Beringer Novel Epigallocatechin Gallate (EGCG) Analogs with Improved Biochemical Properties for Targeting Extracellular and Intracellular <i>Staphylococcus aureus</i> Applied Microbiology antibiotic resistance antibiotic action chemical modification drug design Gram-positive bacteria host–pathogen interaction |
| title | Novel Epigallocatechin Gallate (EGCG) Analogs with Improved Biochemical Properties for Targeting Extracellular and Intracellular <i>Staphylococcus aureus</i> |
| title_full | Novel Epigallocatechin Gallate (EGCG) Analogs with Improved Biochemical Properties for Targeting Extracellular and Intracellular <i>Staphylococcus aureus</i> |
| title_fullStr | Novel Epigallocatechin Gallate (EGCG) Analogs with Improved Biochemical Properties for Targeting Extracellular and Intracellular <i>Staphylococcus aureus</i> |
| title_full_unstemmed | Novel Epigallocatechin Gallate (EGCG) Analogs with Improved Biochemical Properties for Targeting Extracellular and Intracellular <i>Staphylococcus aureus</i> |
| title_short | Novel Epigallocatechin Gallate (EGCG) Analogs with Improved Biochemical Properties for Targeting Extracellular and Intracellular <i>Staphylococcus aureus</i> |
| title_sort | novel epigallocatechin gallate egcg analogs with improved biochemical properties for targeting extracellular and intracellular i staphylococcus aureus i |
| topic | antibiotic resistance antibiotic action chemical modification drug design Gram-positive bacteria host–pathogen interaction |
| url | https://www.mdpi.com/2673-8007/4/4/107 |
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