Comparative transcriptional profiling of tildipirosin-resistant and sensitive Haemophilus parasuis

Lei, Zhixin; Fu, Shulin; Yang, Bing; Liu, Qianying; Ahmed, Saeed; Xu, Lei; Xiong, Jincheng; Cao, Jiyue; Qiu, Yinsheng

doi:10.1038/s41598-017-07972-5

Cited by 12 publications

(16 citation statements)

References 73 publications

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“…The cumulative counts for MIC data, with the exception of one resistant strain with an MIC of 256 μg/ml, were performed to match a suitably shaped normal distribution (normality test, P > 0.200) using SigmaStat and GraphPad Prism software (Figure 3 ). Furthermore, the strain whose MIC was 256 μg/ml had been proved as resistant one, with a resistant HAPS_RS04930 reported by Zhixin Lei [ 49 , 50 ]. The optimum MIC range from 0.002 to 32 μg/ml was obtained from non-linear regression (Table 1 ), and the range was further corrected to 0.032 to 32 μg/ml according to the optimum distribution determined using the NORMINV function in Microsoft Excel.…”

Section: Resultsmentioning

confidence: 99%

“…The high MIC value (256 μg/ml) may be explained by cross-resistance of macrolides, exposure to precursors of tildipirosin (tylosin and tilmicosin) or misuse of tildipirosin. The resistance mechanism of HPS to tildipirosin or other macrolides may be associated with the pathways of amino acid ATP-binding cassette (ABC) transporter system (HAPS_2069, HAPS_RS03630) and the metabolite transporter superfamily (HAPS_2067 and HAPS_2068, HAPS_RS08950) [ 49 , 50 , 55 , 56 ], which will be a focus of future studies. Hence, all HPS isolates (163) except one (256 μg/ml) tested in this study could be considered as a WT isolates for ECV.…”

Section: Discussionmentioning

confidence: 99%

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The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

et al. 2017

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The goal of this study was to establish the epidemiological, pharmacodynamic cut-off values, optimal dose regimens for tildipirosin against Haemophilus parasuis. The minimum inhibitory concentrations (MIC) of 164 HPS isolates were determined and SH0165 whose MIC (2 μg/ml ) were selected for PD analysis. The ex vivo MIC in plasma of SH0165 was 0.25 μg/ml which was 8 times lower than that in TSB. The bacteriostatic, bactericidal and elimination activity (AUC24h/MIC) in serum were 26.35, 52.27 and 73.29 h based on the inhibitory sigmoid Emax modeling. The present study demonstrates that 97.9% of the wild-type (WT) isolates were covered when the epidemiological cut-off value (ECV) was set at 8 μg/ml. The parameters including AUC24h, AUC, T1/2, Cmax, CLb and MRT in PELF were 19.56, 60.41, 2.32, 4.02, 56.6, and 2.63 times than those in plasma, respectively. Regarding the Monte Carlo simulation, the COPD was defined as 0.5 μg/ml in vitro, and the optimal doses to achieve bacteriostatic, bactericidal and elimination effect were 1.85, 3.67 and 5.16 mg/kg for 50% target, respectively, and 2.07, 4.17 and 5.78 mg/kg for 90% target, respectively. The results of this study offer a more optimised alternative for clinical use and demonstrated that 4.17 mg/kg of tildipirosin by intramuscular injection could have an effect on bactericidal activity against HPS. These values are of great significance for the effective treatment of HPS infections, but it also be deserved to be validated in clinical practice in the future research.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

et al. 2017

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“…The Monte Carlo simulation to predict dosage for clinical use had the advantage of taking into account the PK‐PD parameters based on bacteriological outcome. Furthermore, it could set target percentages such as 90% and 50% for simulation models for all data in relation to incidence in pigs (Dorey et al., ; Lei et al., ). As a matter of fact, the products containing dox as an active ingredient must have the posology regimen (dose and length of treatment) on the label in a general against all pathogenic bacteria not specifically for H. parasuis .…”

Section: Discussionmentioning

confidence: 99%

“…Haemophilus parasuis is a Gram‐negative opportunistic pathogen of pigs mainly responsible for pneumonia, and causing considerable economic losses to the pig industry worldwide (Lei et al., ; Yang et al., ). The resistant H. parasuis has been reported in Switzerland, the UK, and Spain.…”

Section: Introductionmentioning

confidence: 99%

Integration of pharmacokinetic–pharmacodynamic for dose optimization of doxycycline againstHaemophilus parasuisin pigs

Zhang

Wang

et al. 2018

Vet Pharm & Therapeutics

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The aims of this study were to establish optimal doses of doxycycline (dox) against Haemophilus parasuis on the basis of pharmacokinetic-pharmacodynamic (PK-PD) integration modeling. The infected model was established by intranasal inoculation of organism in pigs and confirmed by clinical signs, blood biochemistry, and microscopic examinations. The recommended dose (20 mg/kg b.w.) was administered in pigs through intramuscular routes for PK studies. The area under the concentration 0- to 24-hr curve (AUC ), elimination half-life (T ), and mean residence time (MRT) of dox in healthy and H. parasuis-infected pigs were 55.51 ± 5.72 versus 57.10 ± 4.89 μg·hr/ml, 8.28 ± 0.91 versus 9.80 ± 2.38 hr, and 8.43 ± 0.27 versus 8.79 ± 0.18 hr, respectively. The minimal inhibitory concentration (MIC) of dox against 40 H. parasuis isolates was conducted through broth microdilution method, the corresponding MIC and MIC were 0.25 and 1 μg/ml, respectively. The Ex vivo growth inhibition data suggested that dox exhibited a concentration-dependent killing mechanism. Based on the observed AUC /MIC values by modeling PK-PD data in H. parasuis-infected pigs, the doses predicted to obtain bacteriostatic, bactericidal, and elimination effects for H. parasuis over 24 hr were 5.25, 8.55, and 10.37 mg/kg for the 50% target attainment rate (TAR), and 7.26, 13.82, and 18.17 mg/kg for 90% TAR, respectively. This study provided a more optimized alternative for clinical use and demonstrated that the dosage 20 mg/kg of dox by intramuscular administration could have an effective bactericidal activity against H. parasuis.

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“…Three subtypes of type I receptor and type III receptor. The TGFβ signaling pathway includes three subtypes of type I, type II and type III receptor 23 . TGFβ1, TGFβ2 and TGFβ3 are very similar in most biological functions, but they may differ greatly in some aspects.…”

Section: -5p Chi-mir-125b-3p Chi-mir-21-5p Chi-mir-143-5p Chi-mmentioning

confidence: 99%

Inner Mongolian Cashmere Goat Secondary Follicle Development Regulation Research Based on mRNA-miRNA Co-analysis

Han

Yang

et al. 2020

Sci Rep

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Inner Mongolia cashmere goats, as an important part of animal husbandry production, play an important role in animal fiber industry. In recent years, scientific research has made a lot of explorations on the molecular regulation mechanism of hair follicle cycle growth, but few studies have been reported on the development of cashmere hair in fetal period. This study was based on the completion of 21 skin samples of mRNA and miRNA sequencing in 7 fetal periods (45 days, 55 days,65 days,75 days,95 days,115 days and 135 days) of the Inner Mongolia Cashmere goat. The target genes of miRNA associated with the development of secondary hair follicles in the cashmere goats were selected through the combination analysis of mRNA and miRNA data. Then the overexpression vector was constructed and the interaction between the miRNA and the target gene was identified by Dual-Luciferase Reporter Gene System. The function and interaction relationship of chi-miR-199a-5p and TGF-β2 were verified by RT-qPCR and western blot at the level of the fibroblasts in Inner Mongolia Cashmere goat. It provides a theoretical basis for further study of miRNA and its target genes regulating the occurrence and development of skin hair follicles. As the result shows, the expression trends of 7 genes (BAMBI, SMAD1, LTBP1, PPP2R1B, ID4, BMP8B and PITX2) and 7 miRNA (chi-miR-17-5p, chi-miR-125b-3p, chi-miR-21-5p, chi-miR-143-5p and chi-miR-106b-5p) in the skin samples for the seven stages of the fetus were shown to be consistent with the sequencing results. the results of sequencing are reliable. The correlation coefficient of TGF-β2 and chi-miR-199a-5p in fetal 45d-135d expression is −0.84, showing a strong negative correlation, The target relationship was preliminarily judged. The results of double luciferase vector report showed that chi-miR-199a-5p significantly decreased the expression of luciferase in TGF-β2 3′UTR, It is determined that there is a reciprocal relationship between them at a specific time. We transfected chi-miR199a-5p-FAM mimics into fibroblasts cultured in vitro from Inner Mongolia cashmere goats. After transfection, the cells were harvested to extract total RNA and protein. The mRNA and protein expression levels of TGF-β2 in fibroblasts were detected by RT-qPCR and western blot. It was verified that chi-miR-199a-5p inhibited TGF-β2 expression at both mRNA and protein translation levels in fibroblasts. At the same time, it was again proved that the TGF-β2 gene is a target gene of chi-miR199a-5p.

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Comparative transcriptional profiling of tildipirosin-resistant and sensitive Haemophilus parasuis

Cited by 12 publications

References 73 publications

The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

Integration of pharmacokinetic–pharmacodynamic for dose optimization of doxycycline againstHaemophilus parasuisin pigs

Inner Mongolian Cashmere Goat Secondary Follicle Development Regulation Research Based on mRNA-miRNA Co-analysis

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