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Article

Synergistic Effect of a Pleuromutilin Derivative with Tetracycline against Streptococcus suis In Vitro and in the Neutropenic Thigh Infection Model

by
Fang Chen
1,†,
Meng-Chao Wei
1,†,
Yi-Dan Luo
1,
Zhen Jin
1,2,* and
You-Zhi Tang
1,2,*
1
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China
2
Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2020, 25(15), 3522; https://doi.org/10.3390/molecules25153522
Submission received: 28 June 2020 / Revised: 25 July 2020 / Accepted: 30 July 2020 / Published: 1 August 2020
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Medicinal Chemistry)
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Abstract

Tetracycline (TET) has been widely used in the treatment of Streptococcus suis (S. suis) infection. However, it was found that the efficacy of many antibiotics in S. suis decreased significantly, especially tetracycline. In this study, GML-12 (a novel pleuromutilin derivative) was used in combination with TET against 12 S. suis isolates. In the checkerboard assay, the TET/GML-12 combination exhibited synergistic and additive effects against S. suis isolates (n = 12). In vitro time-killing assays and in vivo therapeutic experiments were used to confirm the synergistic effect of the TET/GML-12 combination against S. suis strains screened based on an FICI ≤ 0.5. In time-killing assays, the TET/GML-12 combination showed a synergistic effect or an additive effect against three isolates with a bacterial reduction of over 2.4-log10 CFU/mL compared with the most active monotherapy. Additionally, the TET/GML-12 combination displayed potent antimicrobial activity against four isolates in a mouse thigh infection model. These results suggest that the TET/GML-12 combination may be a potential therapeutic strategy for S. suis infection.
Keywords: Streptococcus suis; tetracycline; combination therapy; checkerboard assays; time-killing assays; thigh infection model Streptococcus suis; tetracycline; combination therapy; checkerboard assays; time-killing assays; thigh infection model
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MDPI and ACS Style

Chen, F.; Wei, M.-C.; Luo, Y.-D.; Jin, Z.; Tang, Y.-Z. Synergistic Effect of a Pleuromutilin Derivative with Tetracycline against Streptococcus suis In Vitro and in the Neutropenic Thigh Infection Model. Molecules 2020, 25, 3522. https://doi.org/10.3390/molecules25153522

AMA Style

Chen F, Wei M-C, Luo Y-D, Jin Z, Tang Y-Z. Synergistic Effect of a Pleuromutilin Derivative with Tetracycline against Streptococcus suis In Vitro and in the Neutropenic Thigh Infection Model. Molecules. 2020; 25(15):3522. https://doi.org/10.3390/molecules25153522

Chicago/Turabian Style

Chen, Fang, Meng-Chao Wei, Yi-Dan Luo, Zhen Jin, and You-Zhi Tang. 2020. "Synergistic Effect of a Pleuromutilin Derivative with Tetracycline against Streptococcus suis In Vitro and in the Neutropenic Thigh Infection Model" Molecules 25, no. 15: 3522. https://doi.org/10.3390/molecules25153522

APA Style

Chen, F., Wei, M.-C., Luo, Y.-D., Jin, Z., & Tang, Y.-Z. (2020). Synergistic Effect of a Pleuromutilin Derivative with Tetracycline against Streptococcus suis In Vitro and in the Neutropenic Thigh Infection Model. Molecules, 25(15), 3522. https://doi.org/10.3390/molecules25153522

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