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| Content Provider | frontiers |
|---|---|
| Author | Wang, Jianfeng Liu, Bowen Teng, Zihao Zhou, Xuan Wang, Xiyan Zhang, Bing Lu, Gejin Niu, Xiaodi Yang, Yongjun Deng, Xuming |
| Abstract | The critical roles of sortase A (SrtA) and listeriolysin O (LLO) in Listeria monocytogenes pathogenicity render these two virulence factors as ideal targets for the development of anti-virulence agents against L. monocytogenes infection. Additionally, the structures of SrtA and LLO are highly conserved among the members of sortase enzyme family and cholesterol dependent toxin family. Here, phloretin, a natural polyphenolic compound derived from apples and pears that has little anti-L. monocytogenes activity, was identified to simultaneously inhibit LLO expression and neutralize SrtA catalytic activity. Phloretin neutralized SrtA activity by causing a conformational change in the protein's active pocket, which prevented engagement with its substrate. Treatment with phloretin simultaneously reduced L. monocytogenes invasion into host cells and blocked the escape of vacuole-entrapped L. monocytogenes into cytoplasm. Further, L. monocytogenes-infected mice that received phloretin showed lower mortality, decreased bacterial burden and reduced pathological injury. Our results demonstrate that phloretin is a promising anti-infective therapeutic for infections caused by L. monocytogenes due to its simultaneous targeting of SrtA and LLO, which may result in fewer side effects than those caused by other antibiotics. |
| ISSN | 22352988 |
| DOI | 10.3389/fcimb.2017.00009 |
| Volume Number | 7 |
| Journal | Frontiers in Cellular and Infection Microbiology |
| Language | English |
| Publisher Date | 2017-01-19 |
| Access Restriction | Open |
| Subject Keyword | Listeria monocytogenes Listeriolysin O Sortase A Anti-infective therapy Phloretin |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Immunology Microbiology Microbiology (medical) |
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