Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A
With continuous emergence and widespread of multidrug-resistant Staphylococcus aureus infections, common antibiotics have become ineffective in treating these infections in the clinical setting. Anti-virulence strategies could be novel, effective therapeutic strategies against drug-resistant bacteri...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-09-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6651/10/10/385 |
| _version_ | 1817997350014025728 |
|---|---|
| author | Ping Ouyang Xuewen He Zhong-Wei Yuan Zhong-Qiong Yin Hualin Fu Juchun Lin Changliang He Xiaoxia Liang Cheng Lv Gang Shu Zhi-Xiang Yuan Xu Song Lixia Li Lizi Yin |
| author_facet | Ping Ouyang Xuewen He Zhong-Wei Yuan Zhong-Qiong Yin Hualin Fu Juchun Lin Changliang He Xiaoxia Liang Cheng Lv Gang Shu Zhi-Xiang Yuan Xu Song Lixia Li Lizi Yin |
| author_sort | Ping Ouyang |
| collection | DOAJ |
| description | With continuous emergence and widespread of multidrug-resistant Staphylococcus aureus infections, common antibiotics have become ineffective in treating these infections in the clinical setting. Anti-virulence strategies could be novel, effective therapeutic strategies against drug-resistant bacterial infections. Sortase A (srtA), a transpeptidase in gram-positive bacteria, can anchor surface proteins that play a vital role in pathogenesis of these bacteria. SrtA is known as a potential antivirulent drug target to treat bacterial infections. In this study, we found that erianin, a natural bibenzyl compound, could inhibit the activity of srtA in vitro (half maximal inhibitory concentration—IC50 = 20.91 ± 2.31 μg/mL, 65.7 ± 7.2 μM) at subminimum inhibitory concentrations (minimum inhibitory concentrations—MIC = 512 μg/mL against S. aureus). The molecular mechanism underlying the inhibition of srtA by erianin was identified using molecular dynamics simulation: erianin binds to srtA residues Ile182, Val193, Trp194, Arg197, and Ile199, forming a stable bond via hydrophobic interactions. In addition, the activities of S. aureus binding to fibronectin and biofilm formation were inhibited by erianin, when co-culture with S. aureus. In vivo, erianin could improve the survival in mice that infected with S. aureus by tail vein injection. Experimental results showed that erianin is a potential novel therapeutic compound against S. aureus infections via affecting srtA. |
| first_indexed | 2024-04-14T02:36:51Z |
| format | Article |
| id | doaj.art-a6763bd02af04dfa96d39f7fb5b73ac6 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-14T02:36:51Z |
| publishDate | 2018-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-a6763bd02af04dfa96d39f7fb5b73ac62022-12-22T02:17:25ZengMDPI AGToxins2072-66512018-09-01101038510.3390/toxins10100385toxins10100385Erianin against Staphylococcus aureus Infection via Inhibiting Sortase APing Ouyang0Xuewen He1Zhong-Wei Yuan2Zhong-Qiong Yin3Hualin Fu4Juchun Lin5Changliang He6Xiaoxia Liang7Cheng Lv8Gang Shu9Zhi-Xiang Yuan10Xu Song11Lixia Li12Lizi Yin13College of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaCollege of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, ChinaWith continuous emergence and widespread of multidrug-resistant Staphylococcus aureus infections, common antibiotics have become ineffective in treating these infections in the clinical setting. Anti-virulence strategies could be novel, effective therapeutic strategies against drug-resistant bacterial infections. Sortase A (srtA), a transpeptidase in gram-positive bacteria, can anchor surface proteins that play a vital role in pathogenesis of these bacteria. SrtA is known as a potential antivirulent drug target to treat bacterial infections. In this study, we found that erianin, a natural bibenzyl compound, could inhibit the activity of srtA in vitro (half maximal inhibitory concentration—IC50 = 20.91 ± 2.31 μg/mL, 65.7 ± 7.2 μM) at subminimum inhibitory concentrations (minimum inhibitory concentrations—MIC = 512 μg/mL against S. aureus). The molecular mechanism underlying the inhibition of srtA by erianin was identified using molecular dynamics simulation: erianin binds to srtA residues Ile182, Val193, Trp194, Arg197, and Ile199, forming a stable bond via hydrophobic interactions. In addition, the activities of S. aureus binding to fibronectin and biofilm formation were inhibited by erianin, when co-culture with S. aureus. In vivo, erianin could improve the survival in mice that infected with S. aureus by tail vein injection. Experimental results showed that erianin is a potential novel therapeutic compound against S. aureus infections via affecting srtA.http://www.mdpi.com/2072-6651/10/10/385sortase AStaphylococcus aureuserianininhibitormolecular mechanism |
| spellingShingle | Ping Ouyang Xuewen He Zhong-Wei Yuan Zhong-Qiong Yin Hualin Fu Juchun Lin Changliang He Xiaoxia Liang Cheng Lv Gang Shu Zhi-Xiang Yuan Xu Song Lixia Li Lizi Yin Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A Toxins sortase A Staphylococcus aureus erianin inhibitor molecular mechanism |
| title | Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A |
| title_full | Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A |
| title_fullStr | Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A |
| title_full_unstemmed | Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A |
| title_short | Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A |
| title_sort | erianin against staphylococcus aureus infection via inhibiting sortase a |
| topic | sortase A Staphylococcus aureus erianin inhibitor molecular mechanism |
| url | http://www.mdpi.com/2072-6651/10/10/385 |
| work_keys_str_mv | AT pingouyang erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT xuewenhe erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT zhongweiyuan erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT zhongqiongyin erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT hualinfu erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT juchunlin erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT changlianghe erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT xiaoxialiang erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT chenglv erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT gangshu erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT zhixiangyuan erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT xusong erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT lixiali erianinagainststaphylococcusaureusinfectionviainhibitingsortasea AT liziyin erianinagainststaphylococcusaureusinfectionviainhibitingsortasea |