Clinical Breakpoint of Apramycin to Swine Salmonella and Its Effect on Ileum Flora.

Xinyu Dai,Lingli Huang,Haihong Hao,Jinli Guo,Yufeng Gu,Dapeng Peng,Guyue Cheng

doi:10.3390/ijms23031424

Xinyu Dai, Lingli Huang + Show 5 more

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https://doi.org/10.3390/ijms23031424

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Abstract

The purpose of this study was to establish the clinical breakpoint (CBP) of apramycin (APR) against Salmonella in swine and evaluate its effect on intestinal microbiota. The CBP was established based on three cutoff values of wild-type cutoff value (COWT), pharmacokinetic-pharmadynamic (PK/PD) cutoff value (COPD) and clinical cutoff value (COCL). The effect of the optimized dose regimen based on ex vivo PK/PD study. The evolution of the ileum flora was determined by the 16rRNA gene sequencing and bioinformatics. This study firstly established the COWT, COPD in ileum, and COCL of APR against swine Salmonella, the value of these cutoffs were 32 µg/mL, 32 µg/mL and 8 µg/mL, respectively. According to the guiding principle of the Clinical Laboratory Standards Institute (CLSI), the final CBP in ileum was 32 µg/mL. Our results revealed the main evolution route in the composition of ileum microbiota of diarrheic piglets treated by APR. The change of the abundances of Bacteroidetes and Euryarchaeota was the most obvious during the evolution process. Methanobrevibacter, Prevotella, S24-7 and Ruminococcaceae were obtained as the highest abundance genus. The abundance of Methanobrevibacter increased significantly when APR treatment carried and decreased in cure and withdrawal period groups. The abundance of Prevotella in the tested groups was significantly lower than that in the healthy group. A decreased of abundance in S24-7 was observed after Salmonella infection and increased slightly after cure. Ruminococcaceae increased significantly after Salmonella infection and decreased significantly after APR treatment. In addition, the genera of Methanobrevibacter and Prevotella were defined as the key node. Valine, leucine and isoleucine biosynthesis, D-Glutamine and D-glutamate metabolism, D-Alanine metabolism, Peptidoglycan and amino acids biosynthesis were the top five Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the ileum microbiota of piglets during the Salmonella infection and APR treatment process. Our study extended the understanding of dynamic shift of gut microbes during diarrheic piglets treated by APR.

Highlights

Salmonellosis is one of the most frequent foodborne zoonotic diseases, characterised by abdominal cramps, diarrhoea, fever and vomiting, constituting a worldwide major public health concern [1]
The results showed that the MIC50 and MIC90 values for APR against 185 swine Salmonella isolates obtained as 8 and 16 mg/L, and the COWT value for APR of Salmonella was 32 μg/mL
Methanobrevibacter, Prevotella, S24-7 and Ruminococcaceae were obtained as the highest abundance genus

Summary

Introduction

Salmonellosis is one of the most frequent foodborne zoonotic diseases, characterised by abdominal cramps, diarrhoea, fever and vomiting, constituting a worldwide major public health concern [1]. The aminoglycoside antibiotics interfered with translational fidelity by binding to the 30S ribosomal subunit, exhibiting excellent characteristics as broad-spectrum antibacterial agents with desirable bactericidal activity against Gram-negative bacteria and mycobacteria [3,4]. Apramycin (APR), equipping a bicyclic sugar moiety with a monosubstituted deoxystreptamine, is distinct from other aminoglycosides [5]. This distinct structure protects APR from degradation by aminoglycoside modifying enzymes that confer resistance to other aminoglycosides and contributes to offer higher selectivity for bacteria [6]. As a veterinary aminocyclitol aminoglycoside, APR was often used to treat or prevent infections caused by Gram-negative bacteria such as Colibacillosis, Salmonellosis and Enteritis in farm animals [7,8]

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