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

The Synergistic Effect of Nano-Silica with Slag on Frost Resistance of Concrete

The frost resistance of concrete is one of the most important factors for its durability. Supplementary cementitious materials could effectively improve the frost resistance of concrete. On this basis, the synergistic effect of nano-silica (NS) with slag on the frost resistance of concrete is better than the single, which was investigated. Nano-silica and slag were employed as a partial substitute of cement. The effect of these on the related indexes, including the mass loss, relative dynamic elastic modulus and porosity of concrete were measured after specified number of freeze and thaw cycles. Results show that the frost resistance of nano-silica modified concrete was obviously improved. The mass loss of control concrete was 2.5 % after 300 freeze-thaw cycles while that of the nano-silica modified concrete was as low as 1%. Further, the anti-freeze durability factor can reach up to 89.55% for the nano-silica modified concrete. The reasons are that the activity and nucleation effects of nano-silica accelerate the hydration of cement and the filling effect leads to more compact matrix. All of these made concrete better frost resistant. This was also proven by the porosity analysis. When the nano-silica was added, the total porosity of nano-silica modified concrete decreased from 14.57 % to 11.39 % compared with the control concrete. So, the synergistic effect of nanosilica with slag can enhance the frost resistance of concrete and improve its durability

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

Molecular Characterization and Biological Function of a Novel LncRNA CRNG in Swine

Our previous study has showed that a novel gene is differentially expressed in the liver of cyadox-fed piglets, but its sequence and function are unknown. Here, rapid amplification of cDNA ends (RACE) and bioinformatics analysis showed that the novel gene is 953 bp without protein-coding ability and locates in chromosome 11. Hence, we identified the novel gene as long non-coding RNA (lncRNA) and named it cyadox-related novel gene (CRNG). Fluorescence in situ hybridization (FISH) showed that CRNG mainly distributes in cytoplasm. Moreover, microarray assay in combination with CRNG interference and overexpression showed that the differential genes such as ANPEP, KITLG, STAT5A, FOXP3, miR-451, IL-2, IL-10, IL-6, and TNF-α are mainly involved in viral and pathogens infection and the immune-inflammatory responses in PK-15 cells. This work reveals that CRNG might play a role in preventing the host from being infected by pathogens and viruses and exerting immune regulatory effects in the cytoplasm, which may be involved in prophylaxis of cyadox in piglets

Single-Trial EEG-fMRI Reveals the Generation Process of the Mismatch Negativity

Although research on the mismatch negativity (MMN) has been ongoing for 40 years, the generation process of the MMN remains largely unknown. In this study, we used a single-trial electro-encephalography (EEG)-functional magnetic resonance imaging (fMRI) coupling method which can analyze neural activity with both high temporal and high spatial resolution and thus assess the generation process of the MMN. We elicited the MMN with an auditory oddball paradigm while recording simultaneous EEG and fMRI. We divided the MMN into five equal-durational phases. Utilizing the single-trial variability of the MMN, we analyzed the neural generators of the five phases, thereby determining the spatiotemporal generation process of the MMN. We found two distinct bottom-up prediction error propagations: first from the auditory cortex to the motor areas and then from the auditory cortex to the inferior frontal gyrus (IFG). Our results support the regularity-violation hypothesis of MMN generation

CRISPR-cas system:biological function in microbes and its use to treat antimicrobial resistant pathogens

The development of antibiotic resistance in bacteria is a major public health threat. Infection rates of resistant pathogens continue to rise against nearly all antimicrobials, which has led to development of different strategies to combat the antimicrobial resistance. In this review, we discuss how the newly popular CRISPR-cas system has been applied to combat antibiotic resistance in both extracellular and intracellular pathogens. We also review a recently developed method in which nano-size CRISPR complex was used without any phage to target themecAgene. However, there is still challenge to practice these methods in field against emerging antimicrobial resistant pathogens