AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>
<i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i> (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges fro...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/21/11617 |
| _version_ | 1797512414510448640 |
|---|---|
| author | Nina Tsao Ya-Chu Chang Sung-Yuan Hsieh Tang-Chi Li Ching-Chen Chiu Hai-Han Yu Tzu-Ching Hsu Chih-Feng Kuo |
| author_facet | Nina Tsao Ya-Chu Chang Sung-Yuan Hsieh Tang-Chi Li Ching-Chen Chiu Hai-Han Yu Tzu-Ching Hsu Chih-Feng Kuo |
| author_sort | Nina Tsao |
| collection | DOAJ |
| description | <i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i> (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges from 20% to 50% in spite of antibiotics administration. AR-12, a pyrazole derivative, has been reported to inhibit the infection of viruses, intracellular bacteria, and fungi. In this report, we evaluated the bactericidal activities and mechanisms of AR-12 on GAS infection. Our in vitro results showed that AR-12 dose-dependently reduced the GAS growth, and 2.5 μg/mL of AR-12 significantly killed GAS within 2 h. AR-12 caused a remarkable reduction in nucleic acid and protein content of GAS. The expression of heat shock protein DnaK and streptococcal exotoxins was also inhibited by AR-12. Surveys of the GAS architecture by scanning electron microscopy revealed that AR-12-treated GAS displayed incomplete septa and micro-spherical structures protruding out of cell walls. Moreover, the combination of AR-12 and gentamicin had a synergistic antibacterial activity against GAS replication for both in vitro and in vivo infection. Taken together, these novel findings obtained in this study may provide a new therapeutic strategy for invasive GAS infection. |
| first_indexed | 2024-03-10T06:01:29Z |
| format | Article |
| id | doaj.art-3b10fa75f6ff45cbb6cb3ce19297c43e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:01:29Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3b10fa75f6ff45cbb6cb3ce19297c43e2023-11-22T20:55:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211161710.3390/ijms222111617AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>Nina Tsao0Ya-Chu Chang1Sung-Yuan Hsieh2Tang-Chi Li3Ching-Chen Chiu4Hai-Han Yu5Tzu-Ching Hsu6Chih-Feng Kuo7Department of Medical Laboratory Science, College of Medical Science and Technology, I-Shou University, Kaohsiung 824005, TaiwanDepartment of Medical Laboratory Science, College of Medical Science and Technology, I-Shou University, Kaohsiung 824005, TaiwanBioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu 300024, TaiwanDepartment of Medical Laboratory Science, College of Medical Science and Technology, I-Shou University, Kaohsiung 824005, TaiwanDepartment of Medical Laboratory Science, College of Medical Science and Technology, I-Shou University, Kaohsiung 824005, TaiwanDepartment of Biological Science and Technology, College of Medical Science and Technology, I-Shou University, Kaohsiung 824005, TaiwanDepartment of Biological Science and Technology, College of Medical Science and Technology, I-Shou University, Kaohsiung 824005, TaiwanSchool of Medicine, I-Shou University, Kaohsiung 824005, Taiwan<i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i> (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges from 20% to 50% in spite of antibiotics administration. AR-12, a pyrazole derivative, has been reported to inhibit the infection of viruses, intracellular bacteria, and fungi. In this report, we evaluated the bactericidal activities and mechanisms of AR-12 on GAS infection. Our in vitro results showed that AR-12 dose-dependently reduced the GAS growth, and 2.5 μg/mL of AR-12 significantly killed GAS within 2 h. AR-12 caused a remarkable reduction in nucleic acid and protein content of GAS. The expression of heat shock protein DnaK and streptococcal exotoxins was also inhibited by AR-12. Surveys of the GAS architecture by scanning electron microscopy revealed that AR-12-treated GAS displayed incomplete septa and micro-spherical structures protruding out of cell walls. Moreover, the combination of AR-12 and gentamicin had a synergistic antibacterial activity against GAS replication for both in vitro and in vivo infection. Taken together, these novel findings obtained in this study may provide a new therapeutic strategy for invasive GAS infection.https://www.mdpi.com/1422-0067/22/21/11617AR-12group A <i>Streptococcus</i> (GAS)invasive infectionsynergistic effect |
| spellingShingle | Nina Tsao Ya-Chu Chang Sung-Yuan Hsieh Tang-Chi Li Ching-Chen Chiu Hai-Han Yu Tzu-Ching Hsu Chih-Feng Kuo AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i> International Journal of Molecular Sciences AR-12 group A <i>Streptococcus</i> (GAS) invasive infection synergistic effect |
| title | AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i> |
| title_full | AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i> |
| title_fullStr | AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i> |
| title_full_unstemmed | AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i> |
| title_short | AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i> |
| title_sort | ar 12 has a bactericidal activity and a synergistic effect with gentamicin against group a i streptococcus i |
| topic | AR-12 group A <i>Streptococcus</i> (GAS) invasive infection synergistic effect |
| url | https://www.mdpi.com/1422-0067/22/21/11617 |
| work_keys_str_mv | AT ninatsao ar12hasabactericidalactivityandasynergisticeffectwithgentamicinagainstgroupaistreptococcusi AT yachuchang ar12hasabactericidalactivityandasynergisticeffectwithgentamicinagainstgroupaistreptococcusi AT sungyuanhsieh ar12hasabactericidalactivityandasynergisticeffectwithgentamicinagainstgroupaistreptococcusi AT tangchili ar12hasabactericidalactivityandasynergisticeffectwithgentamicinagainstgroupaistreptococcusi AT chingchenchiu ar12hasabactericidalactivityandasynergisticeffectwithgentamicinagainstgroupaistreptococcusi AT haihanyu ar12hasabactericidalactivityandasynergisticeffectwithgentamicinagainstgroupaistreptococcusi AT tzuchinghsu ar12hasabactericidalactivityandasynergisticeffectwithgentamicinagainstgroupaistreptococcusi AT chihfengkuo ar12hasabactericidalactivityandasynergisticeffectwithgentamicinagainstgroupaistreptococcusi |