Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress Staphylococcus aureus virulence
Staphylococcus aureus sortase A can anchor virulence proteins, which are responsible for bacterial adhesion, biofilm formation, and inflammation, to the cell membrane surface. The ability of β-lactam antibiotics to combat S. aureus infections is limited by the presence of β-lactamases in this pathog...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1537564/full |
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| author | Fei Teng Lihui Wang Jingyao Wen Zizeng Tian Guizhen Wang Liping Peng |
| author_facet | Fei Teng Lihui Wang Jingyao Wen Zizeng Tian Guizhen Wang Liping Peng |
| author_sort | Fei Teng |
| collection | DOAJ |
| description | Staphylococcus aureus sortase A can anchor virulence proteins, which are responsible for bacterial adhesion, biofilm formation, and inflammation, to the cell membrane surface. The ability of β-lactam antibiotics to combat S. aureus infections is limited by the presence of β-lactamases in this pathogen. In this study, we determined that epicatechin gallate (ECG) and its analogues inhibited the transpeptidase activity of sortase A by interacting with it directly, and the biofilm formation and adhesion abilities of the bacterium decreased after treatment with ECG and its analogues. Additionally, ECG bound to β-lactamase and reduced its ability to hydrolyze nitrocefin. Furthermore, ECG synergized with ampicillin (Amp), enhancing its bactericidal effects and inhibiting the formation of persisters. ECG did not affect the expression of sortase A or β-lactamase but significantly alleviated the cytotoxicity of S. aureus USA300. ECG alone or combined with Amp in vivo improved the survival of mice infected with S. aureus USA300, alleviated pathological tissue damage and pulmonary edema, and reduced the extent of inflammation and level of colonization. The results of this study indicate that the active ingredients of green tea, especially ECG, have the potential to be developed as anti-S. aureus infection agents. |
| format | Article |
| id | doaj-art-d4938b63e55e4e11b2004c2748968a17 |
| institution | Kabale University |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-d4938b63e55e4e11b2004c2748968a172025-08-20T03:40:33ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-03-011510.3389/fcimb.2025.15375641537564Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress Staphylococcus aureus virulenceFei Teng0Lihui Wang1Jingyao Wen2Zizeng Tian3Guizhen Wang4Liping Peng5Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, ChinaDepartment of Respiratory Medicine, The First Hospital of Jilin University, Changchun, ChinaCollege of Biological and Food Engineering, Jilin Engineering Normal University, Changchun, ChinaCollege of Biological and Food Engineering, Jilin Engineering Normal University, Changchun, ChinaCollege of Biological and Food Engineering, Jilin Engineering Normal University, Changchun, ChinaDepartment of Respiratory Medicine, The First Hospital of Jilin University, Changchun, ChinaStaphylococcus aureus sortase A can anchor virulence proteins, which are responsible for bacterial adhesion, biofilm formation, and inflammation, to the cell membrane surface. The ability of β-lactam antibiotics to combat S. aureus infections is limited by the presence of β-lactamases in this pathogen. In this study, we determined that epicatechin gallate (ECG) and its analogues inhibited the transpeptidase activity of sortase A by interacting with it directly, and the biofilm formation and adhesion abilities of the bacterium decreased after treatment with ECG and its analogues. Additionally, ECG bound to β-lactamase and reduced its ability to hydrolyze nitrocefin. Furthermore, ECG synergized with ampicillin (Amp), enhancing its bactericidal effects and inhibiting the formation of persisters. ECG did not affect the expression of sortase A or β-lactamase but significantly alleviated the cytotoxicity of S. aureus USA300. ECG alone or combined with Amp in vivo improved the survival of mice infected with S. aureus USA300, alleviated pathological tissue damage and pulmonary edema, and reduced the extent of inflammation and level of colonization. The results of this study indicate that the active ingredients of green tea, especially ECG, have the potential to be developed as anti-S. aureus infection agents.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1537564/fullECGsortase Aβ-lactamasebiofilmpersistersStaphylococcus aureus |
| spellingShingle | Fei Teng Lihui Wang Jingyao Wen Zizeng Tian Guizhen Wang Liping Peng Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress Staphylococcus aureus virulence Frontiers in Cellular and Infection Microbiology ECG sortase A β-lactamase biofilm persisters Staphylococcus aureus |
| title | Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress Staphylococcus aureus virulence |
| title_full | Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress Staphylococcus aureus virulence |
| title_fullStr | Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress Staphylococcus aureus virulence |
| title_full_unstemmed | Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress Staphylococcus aureus virulence |
| title_short | Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress Staphylococcus aureus virulence |
| title_sort | epicatechin gallate and its analogues interact with sortase a and β lactamase to suppress staphylococcus aureus virulence |
| topic | ECG sortase A β-lactamase biofilm persisters Staphylococcus aureus |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1537564/full |
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