Fluoroquinolone Resistance in <i>Salmonella</i>: Mechanisms, Fitness, and Virulence

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Fluoroquinolone Resistance in <i>Salmonella</i>: Mechanisms, Fitness, and Virulence

Fluoroquinolones are highly effective broad-spectrum antibiotics usually used for the treatment of human and animal infections, including salmonellosis. Fluoroquinolones act against Salmonella by inhibiting their DNA replication. However, several zoonotic serotypes of Salmonella have developed resistance or are less susceptible to fluoroquinolones. Salmonella presents its resistance by substituting amino acids within the topoisomerase subunits, overexpression of multidrug efflux pumps, or decreasing the expression of outer membrane porins. The resistance level is further increased with the plasmid-mediated quinolone resistance genes which could horizontally transfer the resistance from strain to strain. The development of resistance in Salmonella shows that it is a multifactorial process and the acquisition of fluoroquinolone resistance might have significant influences on the bacterial fitness and virulence. Due to the high level resistance against fluoroquinolones that has been observed in Salmonella, care needs to be taken to avoid misuse and overuse of this important class of antibiotics to minimize the occurrence and dissemination of resistance

Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model

Robust model of fresh jujube soluble solids content with near-infrared (NIR) spectroscopy

A robust partial least square (PLS) calibration model with high accuracy and stability was established for the measurement of soluble solids content (SSC) of fresh jujube using near-infrared (NIR) spectroscopytechnique. Fresh jujube samples were collected in different areas of Taigu and Taiyuan cities, central China in 2008 and 2009. A partial least squares (PLS) calibration model was established based on the NIR spectra of 70 fresh jujube samples collected in 2008. A good calibration result was obtained with correlation coefficient (Rc) of 0.9530 and the root mean square error of calibration (RMSEC) of 0.3951 °Brix. Another PLS calibration model was established based on the NIR spectral of 180 samples collected in 2009; it resulted in the Rc of 0.8536 and the RMSEC of 1.1410 °Brix. It could be seen that the accuracy of established PLS models were different when samples harvested in different years were used for the model calibration. In order to improve the accuracy and robustness of model, different numbers (5, 10, 15, 20, 30 and 40) of samples harvested in 2008 were added to the calibration sample set of the model with samples harvested in 2009, respectively. The established PLS models obtained Rc with the range of 0.8846 to 0.8893 and RMSEC with the range of 1.0248 to 0.9645 °Brix. The obtained results werebetter than the result of the model which was established only with samples harvested in 2009. Moreover, the models established using different numbers of added samples had similar results. Therefore, it was concluded that adding samples from another harvest year could improve the accuracy and robustness of the model for SSC prediction of fresh jujube. The overall results proved that the consideration of samples from different harvest places and years would be useful for establishing an accuracy and robustness spectral model.Keywords: Near-infrared (NIR) spectroscopy, Huping jujube, soluble solids content (SSC), partial least squares (PLS), accuracy, stabilit

Mutational and Transcriptomic Changes Involved in the Development of Macrolide Resistance in Campylobacter jejuni

Macrolide antibiotics are important for clinical treatment of infections caused by Campylobacter jejuni. Development of resistance to this class of antibiotics in Campylobacter is a complex process, and the dynamic molecular changes involved in this process remain poorly defined. Multiple lineages of macrolide-resistant mutants were selected by stepwise exposure of C. jejuni to escalating doses of erythromycin or tylosin. Mutations in target genes were determined by DNA sequencing, and the dynamic changes in the expression of antibiotic efflux transporters and the transcriptome of C. jejuni were examined by real-time reverse transcription-PCR, immunoblotting, and DNA microarray analysis. Multiple types of mutations in ribosomal proteins L4 and L22 occurred early during stepwise selection. On the contrary, the mutations in the 23S rRNA gene, mediating high resistance to macrolides, were observed only in the late-stage mutants. Upregulation of antibiotic efflux genes was observed in the intermediately resistant mutants, and the magnitude of upregulation declined with the occurrence of mutations in the 23S rRNA gene. DNA microarray analysis revealed the differential expression of 265 genes, most of which occurred in the intermediate mutant, including the upregulation of genes encoding ribosomal proteins and the downregulation of genes involved in energy metabolism and motility. These results indicate (i) that mutations in L4 and L22 along with temporal overexpression of antibiotic efflux genes precede and may facilitate the development of high-level macrolide resistance and (ii) that the development of macrolide resistance affects the pathways important for physiology and metabolism in C. jejuni, providing an explanation for the reduced fitness of macrolide-resistant Campylobacter

The Involvement of the Cas9 Gene in Virulence of Campylobacter jejuni

Campylobacter jejuni is considered as the leading cause of gastroenteritis all over the world. This bacterium has the CRISPR–cas9 system, which is used as a gene editing technique in different organisms. However, its role in bacterial virulence has just been discovered; that discovery, however, is just the tip of the iceberg. The purpose of this study is to find out the relationship between cas9 and virulence both phenotypically and genotypically in C. jejuni NCTC11168. Understanding both aspects of this relationship allows for a much deeper understanding of the mechanism of bacterial pathogenesis. The present study determined virulence in wild and mutant strains by observing biofilm formation, motility, adhesion and invasion, intracellular survivability, and cytotoxin production, followed by the transcriptomic analysis of both strains. The comparative gene expression profile of wild and mutant strains was determined on the basis of De-Seq transcriptomic analysis, which showed that the cas9 gene is involved in enhancing virulence. Differential gene expression analysis revealed that multiple pathways were involved in virulence, regulated by the CRISPR-cas9 system. Our findings help in understanding the potential role of cas9 in regulating the other virulence associated genes in C. jejuni NCTC11168. The findings of this study provide critical information about cas9's potential involvement in enhancing the virulence of C. jejuni, which is a major public health threat

CGRP Regulates the Age-Related Switch Between Osteoblast and Adipocyte Differentiation

Osteoporosis is a chronic age-related disease. During aging, bone marrow-derived mesenchymal stem cells (BMSCs) display increased adipogenic, along with decreased osteogenic, differentiation capacity. The aim of the present study was to investigate the effect of calcitonin gene-related peptide (CGRP) on the osteogenic and adipogenic differentiation potential of BMSC-derived osteoblasts. Here, we found that the level of CGRP was markedly lower in bone marrow supernatant from aged mice compared with that in young mice. In vitro experiments indicated that CGRP promoted the osteogenic differentiation of BMSCs while inhibiting their adipogenic differentiation. Compared with vehicle-treated controls, aged mice treated with CGRP showed a substantial promotion of bone formation and a reduction in fat accumulation in the bone marrow. Similarly, we found that CGRP could significantly enhance bone formation in ovariectomized (OVX) mice in vivo. Together, our results suggested that CGRP may be a key regulator of the age-related switch between osteogenesis and adipogenesis in BMSCs and may represent a potential therapeutic strategy for the treatment of age-related bone loss

Interferon regulatory factor 2 binding protein 2b regulates neutrophil versus macrophage fate during zebrafish definitive myelopoiesis

International audienceInterferon regulatory factor 2 binding protein 2b regulates neutrophil versus macrophage fate during zebrafish definitive myelopoiesis