The therapeutic effect of Chlorogenic acid against Staphylococcus aureus infection through Sortase A inhibition
The emergence and wide spread of multi-drug resistant Staphylococcus aureus (S. aureus) requires the development of new therapeutic agents with alternative modes of action. Anti-virulence strategies are hoped to meet that need. Sortase A (SrtA) has attracted great interest as a potential drug target...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2015-10-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01031/full |
| _version_ | 1818196722388566016 |
|---|---|
| author | Lin eWang Chongwei eBi Hongjun eCai Bingrun eLiu Xiaobo eZhong Xuming eDeng Xiaodi eNiu Dacheng eWang |
| author_facet | Lin eWang Chongwei eBi Hongjun eCai Bingrun eLiu Xiaobo eZhong Xuming eDeng Xiaodi eNiu Dacheng eWang |
| author_sort | Lin eWang |
| collection | DOAJ |
| description | The emergence and wide spread of multi-drug resistant Staphylococcus aureus (S. aureus) requires the development of new therapeutic agents with alternative modes of action. Anti-virulence strategies are hoped to meet that need. Sortase A (SrtA) has attracted great interest as a potential drug target to treat infections caused by S. aureus, as many of the surface proteins displayed by SrtA function as virulence factors by mediating bacterial adhesion to specific organ tissues, invasion of host cells, and evasion of the host-immune responses. It has been suggested that inhibitors of SrtA might be promising candidates for the treatment and/or prevention of S. aureus infections. In this study, we report that Chlorogenic acid (CHA), a natural compound that lacks significant anti–S. aureus activity, inhibit the activity of SrtA in vitro (IC50=33.86±5.55μg/ml) and the binding of S. aureus to fibrinogen (Fg). Using molecular dynamics simulations and mutagenesis assays, we further demonstrate that CHA binds to the binding sites of C184 and G192 in the SrtA. In vivo studies demonstrated that CHA prevent mice from S. aureus-induced renal abscess, resulting in a significant survival advantage. These findings indicate that CHA is a promising therapeutic compound against SrtA during S. aureus infections. |
| first_indexed | 2024-12-12T01:38:36Z |
| format | Article |
| id | doaj.art-262c8f40bcd442a8a93c146361aa1e83 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-12T01:38:36Z |
| publishDate | 2015-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-262c8f40bcd442a8a93c146361aa1e832022-12-22T00:42:47ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2015-10-01610.3389/fmicb.2015.01031163560The therapeutic effect of Chlorogenic acid against Staphylococcus aureus infection through Sortase A inhibitionLin eWang0Chongwei eBi1Hongjun eCai2Bingrun eLiu3Xiaobo eZhong4Xuming eDeng5Xiaodi eNiu6Dacheng eWang7Jilin UniversityJilin UniversityJilin Agricultural UniversityJilin UniversityJilin UniversityJilin UniversityJilin UniversityJilin UniversityThe emergence and wide spread of multi-drug resistant Staphylococcus aureus (S. aureus) requires the development of new therapeutic agents with alternative modes of action. Anti-virulence strategies are hoped to meet that need. Sortase A (SrtA) has attracted great interest as a potential drug target to treat infections caused by S. aureus, as many of the surface proteins displayed by SrtA function as virulence factors by mediating bacterial adhesion to specific organ tissues, invasion of host cells, and evasion of the host-immune responses. It has been suggested that inhibitors of SrtA might be promising candidates for the treatment and/or prevention of S. aureus infections. In this study, we report that Chlorogenic acid (CHA), a natural compound that lacks significant anti–S. aureus activity, inhibit the activity of SrtA in vitro (IC50=33.86±5.55μg/ml) and the binding of S. aureus to fibrinogen (Fg). Using molecular dynamics simulations and mutagenesis assays, we further demonstrate that CHA binds to the binding sites of C184 and G192 in the SrtA. In vivo studies demonstrated that CHA prevent mice from S. aureus-induced renal abscess, resulting in a significant survival advantage. These findings indicate that CHA is a promising therapeutic compound against SrtA during S. aureus infections.http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01031/fullChlorogenic AcidStaphylococcus aureusBinding siteinhibitorRenal abscessSortase A |
| spellingShingle | Lin eWang Chongwei eBi Hongjun eCai Bingrun eLiu Xiaobo eZhong Xuming eDeng Xiaodi eNiu Dacheng eWang The therapeutic effect of Chlorogenic acid against Staphylococcus aureus infection through Sortase A inhibition Frontiers in Microbiology Chlorogenic Acid Staphylococcus aureus Binding site inhibitor Renal abscess Sortase A |
| title | The therapeutic effect of Chlorogenic acid against Staphylococcus aureus infection through Sortase A inhibition |
| title_full | The therapeutic effect of Chlorogenic acid against Staphylococcus aureus infection through Sortase A inhibition |
| title_fullStr | The therapeutic effect of Chlorogenic acid against Staphylococcus aureus infection through Sortase A inhibition |
| title_full_unstemmed | The therapeutic effect of Chlorogenic acid against Staphylococcus aureus infection through Sortase A inhibition |
| title_short | The therapeutic effect of Chlorogenic acid against Staphylococcus aureus infection through Sortase A inhibition |
| title_sort | therapeutic effect of chlorogenic acid against staphylococcus aureus infection through sortase a inhibition |
| topic | Chlorogenic Acid Staphylococcus aureus Binding site inhibitor Renal abscess Sortase A |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01031/full |
| work_keys_str_mv | AT linewang thetherapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT chongweiebi thetherapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT hongjunecai thetherapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT bingruneliu thetherapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT xiaoboezhong thetherapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT xumingedeng thetherapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT xiaodieniu thetherapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT dachengewang thetherapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT linewang therapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT chongweiebi therapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT hongjunecai therapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT bingruneliu therapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT xiaoboezhong therapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT xumingedeng therapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT xiaodieniu therapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition AT dachengewang therapeuticeffectofchlorogenicacidagainststaphylococcusaureusinfectionthroughsortaseainhibition |