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

Fang Chen,Yi-Dan Luo,Meng-Chao Wei,Zhen Jin,You-Zhi Tang

doi:10.3390/molecules25153522

Fang Chen, Yi-Dan Luo + Show 3 more

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https://doi.org/10.3390/molecules25153522

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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.

Highlights

Streptococcus suis (S. suis) is a significant zoonotic pathogen that causes a variety of diseases, ranging from meningitis to serious blood infections, and an impact on human health with deafness [1,2].People who usually come in contact with infected pigs or pork-derived products are at risk, such as pig farmers, slaughterhouse workers and veterinarians [3]
Most S. suis strains were resistant to TET (MIC50 = 64 μg/mL)
To further study the antibacterial effect of TET combined with GML-12, we evaluated the in vitro killing activities of two drugs against S. suis

Summary

Introduction

Streptococcus suis (S. suis) is a significant zoonotic pathogen that causes a variety of diseases, ranging from meningitis to serious blood infections, and an impact on human health with deafness [1,2].People who usually come in contact with infected pigs or pork-derived products are at risk, such as pig farmers, slaughterhouse workers and veterinarians [3]. Streptococcus suis (S. suis) is a significant zoonotic pathogen that causes a variety of diseases, ranging from meningitis to serious blood infections, and an impact on human health with deafness [1,2]. In China, two large outbreaks of human S. suis infection occurred in 1998 and 2005 [4,5]. S. suis infections in human have been reported from over 30 countries, and the number of cases has continued to rise in recent decades [6]. It poses a significant threat to public health and causes considerable economic losses in the pig industry [7]. Various types of vaccines have been developed to prevent S. suis strains infection, but their preventive efficacy was not stable [8,9]. Considering the economic benefits and therapeutic effects, the use of antibiotics was the first choice against S. suis [10]

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