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Molecules (Basel, Switzerland) Dec 2020The ability of to produce virulence factors, such as biofilm, added to its increased resistance to antimicrobials can cause infections that are difficult to treat. Many...
The ability of to produce virulence factors, such as biofilm, added to its increased resistance to antimicrobials can cause infections that are difficult to treat. Many staphylococcal virulence factors are under the control of the accessory gene regulator (). The objective of this study was to establish the locus and susceptibility of biofilm-producing specimens to antimicrobial agents, through PCR reactions, reverse transcription polymerase chain reaction (RT-PCR), and the determination of minimum inhibitory concentration (MIC), and to analyze the clonal profile of 300 strains isolated from blood culture specimens from inpatients at a University Hospital in Brazil, over a 20-year period by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) techniques. The operon expression was shown in 83.6% strains, gene in 11.5%, and gene in 32.8%. Oxacillin resistance was detected in 90.1%, while 4.9% showed tigecycline resistance, and intermediate resistance to quinupristin/dalfopristin was identified in 0.4%. Clonal profile determination showed 11 clusters, with the ST2 type determined as the major cluster. The biofilm producer demonstrated a predominance of I locus, oxacillin resistance, and SCC III as well as the potential dissemination of pathogenic clones in hospital settings over long periods.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Brazil; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Staphylococcal Infections; Staphylococcus epidermidis; Virginiamycin
PubMed: 33287389
DOI: 10.3390/molecules25235715 -
Animals : An Open Access Journal From... Dec 2020This study investigated the effects of () use on growth performance, serum immunity, intestinal morphology, and microbiota as an antibiotic alternative in weaned...
This study investigated the effects of () use on growth performance, serum immunity, intestinal morphology, and microbiota as an antibiotic alternative in weaned piglets. Over the course of 28 days, 120 piglets were allocated to four treatments with six replicates of five piglets each. The treatments were: CON (basal diet); AGP (basal diet supplemented with 0.075 g/kg chlortetracycline, 0.055 g/kg kitasamycin, and 0.01 g/kg virginiamycin); CBN (basal diet supplemented with normal dosage of 2.5 × 10 CFU/kg ); and CBH (basal diet supplemented with high dosage of 2.5 × 10 CFU/kg ). Body weight (BW) and feed consumption were recorded at the beginning and on days 14 and 28 of the experiment, and representative feed samples and fresh feces were collected from each pen between days 26 and 28. Average fecal score of diarrhea was visually assessed each morning during the experimental period. On the morning of days 14 and 28, blood samples were collected to prepare serum for immune and antioxidant parameters measurement. One male piglet close to the average group BW was selected from each replicate and was slaughtered on day 21 of the experiment. Intestinal crypt villi, and colonic microbiota and its metabolites short-chain fatty acids were measured. Compared to the CON group, the CBN and AGP groups significantly decreased ( < 0.05) the ratio of feed to weight gain by 8.86% and 8.37% between days 1 and 14, 3.96% and 13.36% between days 15 and 28, 5.47% and 11.44% between days 1 and 28. Dietary treatment with and AGPs significantly decreased the average fecal score during the experimental period ( < 0.05). The apparent total tract digestibility of dry matter, organic matter, and total carbohydrates in the CBH group were higher respectively at 3.27%, 2.90%, and 2.97%, than those in the CON or AGP groups ( < 0.05). Compared to the CON group, the CBH group significantly increased short-chain fatty acids in colon and villus height in the jejunum ( < 0.05). The CBN group had higher serum levels of immunoglobulins, interleukin 2 (IL-2), and glutathione peroxidase (GSH-PX) activity, but lower serum levels of IL-1β and IL-6, and a lower aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (γ-GT) activity ( < 0.05), while compared to the CON group. Dietary treatment with significantly increased the relative abundance of and ( < 0.05). In summary, diet with increased the growth performance and benefited the health of weaned piglets.
PubMed: 33287332
DOI: 10.3390/ani10122287 -
Preventive Veterinary Medicine Jan 2021Campylobacter infections in humans are usually self-limiting; however, antibiotic intervention may be necessary in the case of severe infection. Fluoroquinolones are...
Campylobacter infections in humans are usually self-limiting; however, antibiotic intervention may be necessary in the case of severe infection. Fluoroquinolones are often the drug of choice for treatment of campylobacteriosis; however, resistance to these drugs can develop rapidly, complicating treatment protocols. Increasing resistance to fluoroquinolones in human infections has coincided with approval of use of fluoroquinolones in animals, therefore, isolation of fluoroquinolone resistant (FQr) Campylobacter in broiler flocks is concerning. This cross-sectional study utilized data collected from 2013-2018 by the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) on-farm surveillance program to investigate prevalence factors associated with the isolation of FQr C. jejuni from broiler faecal samples. Mixed effects logistic regression models accounting for clustering of flocks within hatcheries, with and without a fixed effect for the presence of flock level tetracycline resistance were used to assess prevalence factors among 536 C. jejuni isolates from 158 flocks. Both models indicated that the type of bird used (Ross versus Cobb or mixed), the use of virginiamycin as a feed additive, the use of traps to control rodent populations in the barn, and the total number of birds in the barn were significant prevalence factors for increased FQr C. jejuni in a flock. In the model where flock level tetracycline resistance was included as a fixed effect, the odds of FQr C. jejuni increased by 16 (95% CI: 3.74, 68), and the magnitude of the effect of each of the identified prevalence factors was larger. Both models indicated that methods of disinfection of water lines between production cycles is important, with the use of chlorine being protective in the model where tetracycline resistance was included as a fixed effect, and the use of hydrogen peroxide being a risk factor in the model where tetracycline resistance was not included as a fixed effect. The use of hot water to wash the barn between production cycles was also a significant protective factor in the model where tetracycline resistance was not included as a fixed effect. These results indicate that biosecurity and sanitation procedures play a role in the dissemination of FQr C. jejuni in broiler flocks. Future analysis should seek to understand the effect of different disinfectant products on the isolation of FQr C. jejuni. Gaining a better understanding of the management of these critical practices may allow for the reduction of this enteric pathogen in broiler flocks in Canada.
Topics: Animals; Anti-Bacterial Agents; Campylobacter Infections; Campylobacter jejuni; Canada; Cross-Sectional Studies; Drug Resistance, Bacterial; Fluoroquinolones; Microbial Sensitivity Tests; Poultry Diseases; Prevalence
PubMed: 33285388
DOI: 10.1016/j.prevetmed.2020.105164 -
Poultry Science Dec 2020The negative effects of dietary antibiotics have become a widespread concern. It is imperative to search for a new type of green, safe, and efficient feed additive that...
The negative effects of dietary antibiotics have become a widespread concern. It is imperative to search for a new type of green, safe, and efficient feed additive that can replace antibiotics. This study was to investigate the effects of glucose oxidase (GOD) on growth performance, immune function, and intestinal barrier in ducks infected with Escherichia coli O88. First, we established the E. coli challenge model of ducks through a preliminary experiment and then carried out the formal experiment by using 144 1-day-old male lean Peking ducklings (50 ± 2.75 g). All ducks were randomly assigned to 1 of 3 dietary treatment groups of basal diet (control), 30 mg/kg virginiamycin (antibiotic), and 200 U/kg GOD (1,000 U/g). Each group consisted of 6 replications with 8 birds per replicate. At day 7, all ducks were orally administered 0.2 mL E coli O88 (3 × 10 cfu/mL) twice, 8 h apart based on the preliminary experiment. The experiment lasted for 28 d. Dietary supplementation with GOD improved growth performance of ducks infected with E. coli. The GOD increased contents of Ig in plasma and secreted Ig A in jejunal mucosa. The GOD group had lower concentrations of inflammatory cytokines (tumor necrosis factor-α, IL-1β, and IL-6) and their upstream regulator Toll-like receptor 4 in the jejunum of ducks than the control group. Supplementation with GOD increased villus height and decreased crypt depth in the jejunum. The gene expression of tight junction proteins (zonula occludens-1, claudin-1 and claudin-2) was enhanced by adding GOD. The GOD decreased intestinal permeability by reducing the concentrations of diamine oxidase and D-lactic in plasma of ducks. There were no significant differences in almost all the indices tested between the GOD and the antibiotic groups. In conclusion, supplementation of GOD improved growth performance, immune function, and intestinal barrier of ducks infected with E. coli O88. Glucose oxidase may serve as a promising alternative therapy to antibiotics to relieve or prevent colibacillosis in ducks.
Topics: Animals; Diet; Dietary Supplements; Ducks; Escherichia coli; Escherichia coli Infections; Glucose Oxidase; Immunity; Intestinal Mucosa; Male; Poultry Diseases; Random Allocation
PubMed: 33248570
DOI: 10.1016/j.psj.2020.09.038 -
Microorganisms Nov 2020The aim of the present study was to investigate variation in antimicrobial resistance in () isolated from chickens after withdrawal of antimicrobial growth promoters...
The aim of the present study was to investigate variation in antimicrobial resistance in () isolated from chickens after withdrawal of antimicrobial growth promoters (AGPs); and to investigate the correlation between the presence of toxin genes (, , and ) and antimicrobial resistance. Altogether, 162 isolates of were obtained from chickens displaying clinical signs of necrotic enteritis ( = 65) and from healthy chickens ( = 97) in Korea during 2010-2016. Compared to before AGP withdrawal, increased antimicrobial resistance or MIC/MIC value was observed for nine antimicrobials including penicillin, tetracycline, tylosin, erythromycin, florfenicol, enrofloxacin, monensin, salinomycin, and maduramycin. Significantly ( < 0.05) higher resistance to gentamicin, clindamycin, and virginiamycin was found in isolates from chickens with necrotic enteritis compared to those from healthy chickens. gene was not detected in isolates from healthy chickens. A correlation between toxin gene prevalence and antibiotic resistance was found in the isolates. Because the usage of antimicrobials may contribute to the selection of both resistance and toxin genes, these can potentially make it challenging to control antimicrobial resistance in pathogenic colonies. Therefore, a more complete understanding of the interplay between resistance and virulence genes is required.
PubMed: 33228100
DOI: 10.3390/microorganisms8111825 -
Animals : An Open Access Journal From... Oct 2020Medium-chain fatty acid glycerides have been shown to provide energy for rapid oxidation in the body. The study was conducted to investigate the effects of dietary...
Medium-chain fatty acid glycerides have been shown to provide energy for rapid oxidation in the body. The study was conducted to investigate the effects of dietary supplementation with medium-chain fatty acid glyceride on the growth performance and intestinal health of weaned piglets fed with a low-protein diet. Nighty healthy weaned piglets were randomly divided into five treatments: NP (Normal protein treatment, normal-protein diet no antibiotics included); NC (Negative control, low-protein diet no antibiotics included); PC (Positive control, low-protein diet +75 mg/kg quinocetone, 20 mg/kg virginiamycin and 50 mg/kg aureomycin); MCT (tricaprylin + tricaprin treatment, low-protein diet + tricaprylin + tricaprin); GML (glycerol monolaurate treatment, low-protein diet + glycerol monolaurate). The results showed that the average daily feed intake (ADFI) of the MCT treatment was significantly higher than that of the NP, NC treatments ( < 0.05). In the jejunum, the villus height of the GML treatment was significantly lower than that of the PC treatment ( < 0.05), and the number of goblet cells in the GML treatment was higher than that in the NC treatment ( < 0.05). Compared with the NC treatment, the MCT treatment significantly increased the level of claudin-1, Zonula occludens-1(ZO-1), while the GML treatment significantly increased the level of claudin-1, occludin, ZO-1 ( < 0.05). In the ileum, the level of ZO-1 in the GML treatment was significantly higher than that in the NP, NC, PC treatments ( < 0.05). Compared with the NC treatment, the GML treatment significantly increased the level of Secretory immunoglobulin A (SIgA) in the ileum and serum, while the MCT treatment significantly increased the level of SIgA and decreased the level of interleukin-6 (IL-6) in the ileum ( < 0.05). These results showed that the addition of medium-chain fatty acid glycerides to a low-protein diet could improve the growth performance and intestinal functional barrier of weaned piglets and also improve the immune function of weaned piglets.
PubMed: 33053685
DOI: 10.3390/ani10101852 -
Expert Review of Anti-infective Therapy May 2021Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially... (Review)
Review
INTRODUCTION
Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially multidrug-resistant isolates.
AREAS COVERED
This review provides an updated overview of structural and activity characteristics, mechanisms of action and resistance, pharmacokinetic/pharmacodynamic, and clinical use of streptogramins.
EXPERT OPINION
The streptogramin antibiotics act by inhibition of the bacterial protein synthesis. They are composed of two chemically distinct compounds, namely type A and type B streptogramins, which exert a rapid bactericidal activity against a wide range of Gram-positive bacteria (including methicillin-resistant staphylococci and vancomycin-resistant enterococci). Several mechanisms of resistance have been identified in staphylococci and enterococci but the prevalence of streptogramin resistance among clinical isolates remains very low. Even if only a few randomized clinical trials have been conducted, the efficacy of pristinamycin has been largely demonstrated with an extensive use for 50 years in France and some African countries. Despite its effectiveness in the treatment of severe Gram-positive bacterial infections demonstrated in several studies and the low rate of reported resistance, the clinical use of quinupristin-dalfopristin has remained limited, mainly due to its poor tolerance. Altogether, streptogramins (especially pristinamycin) can be considered as potential alternatives for the treatment of Gram-positive infections.
Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Pristinamycin; Randomized Controlled Trials as Topic; Streptogramins; Virginiamycin
PubMed: 33030387
DOI: 10.1080/14787210.2021.1834851 -
Nature Oct 2020Natural products serve as chemical blueprints for most antibiotics in clinical use. The evolutionary process by which these molecules arise is inherently accompanied by...
Natural products serve as chemical blueprints for most antibiotics in clinical use. The evolutionary process by which these molecules arise is inherently accompanied by the co-evolution of resistance mechanisms that shorten the clinical lifetime of any given class of antibiotics. Virginiamycin acetyltransferase (Vat) enzymes are resistance proteins that provide protection against streptogramins, potent antibiotics against Gram-positive bacteria that inhibit the bacterial ribosome. Owing to the challenge of selectively modifying the chemically complex, 23-membered macrocyclic scaffold of group A streptogramins, analogues that overcome the resistance conferred by Vat enzymes have not been previously developed. Here we report the design, synthesis, and antibacterial evaluation of group A streptogramin antibiotics with extensive structural variability. Using cryo-electron microscopy and forcefield-based refinement, we characterize the binding of eight analogues to the bacterial ribosome at high resolution, revealing binding interactions that extend into the peptidyl tRNA-binding site and towards synergistic binders that occupy the nascent peptide exit tunnel. One of these analogues has excellent activity against several streptogramin-resistant strains of Staphylococcus aureus, exhibits decreased rates of acetylation in vitro, and is effective at lowering bacterial load in a mouse model of infection. Our results demonstrate that the combination of rational design and modular chemical synthesis can revitalize classes of antibiotics that are limited by naturally arising resistance mechanisms.
Topics: Acetylation; Acetyltransferases; Animals; Anti-Bacterial Agents; Bacterial Load; Binding Sites; Cryoelectron Microscopy; Drug Design; Drug Resistance, Bacterial; Female; In Vitro Techniques; Mice; Microbial Sensitivity Tests; Models, Molecular; RNA, Transfer; Ribosomes; Staphylococcus aureus; Streptogramin Group A; Virginiamycin
PubMed: 32968273
DOI: 10.1038/s41586-020-2761-3 -
BMC Genetics Sep 2020In order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene...
BACKGROUND
In order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene transcription, 32 weaned piglets were employed as animal models and randomly allocated into two groups with diets supplemented with 0 or LDA (chlorotetracycline and virginiamycin).
RESULTS
During the 4 weeks of the experiment, LDA showed a clear growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. Promoter methylome profiling using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated that most of the 745 differential methylation regions (DMRs) were hypermethylated in the LDA group. Several DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. In addition, 71 differentially expressed genes (DEGs) were obtained by strand-specific transcriptome analysis of liver tissues, including ALOX15, CXCL10 and NNMT, which are three key DEGs that function in lipid metabolism and immunity and which had highly elevated expression in the LDA group. In accordance with these molecular changes, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were downregulated in the LDA group.
CONCLUSIONS
Our results indicate that LDA could induce epigenetic and transcriptional changes of key genes and lead to enhanced efficiency of lipid metabolism in the liver.
Topics: Animals; Anti-Bacterial Agents; DNA Methylation; Diet; Epigenesis, Genetic; Female; Lipid Metabolism; Lipids; Liver; Sus scrofa; Transcriptome; Weight Gain
PubMed: 32957918
DOI: 10.1186/s12863-020-00918-3 -
Antimicrobial Agents and Chemotherapy Oct 2020Vga(A) protein variants confer different levels of resistance to lincosamides, streptogramin A, and pleuromutilins (LSP) by displacing antibiotics from the ribosome....
Vga(A) protein variants confer different levels of resistance to lincosamides, streptogramin A, and pleuromutilins (LSP) by displacing antibiotics from the ribosome. Here, we show that expression of (A) variants from is regulated by -regulatory RNA in response to the LSP antibiotics by the mechanism of ribosome-mediated attenuation. The specificity of induction depends on Vga(A)-mediated resistance rather than on the sequence of the riboregulator. Fine tuning between Vga(A) activity and its expression in response to the antibiotics may contribute to the selection of more potent Vga(A) variants because newly acquired mutation can be immediately phenotypically manifested.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Lincosamides; Macrolides; Ribosomes; Streptogramin A
PubMed: 32816732
DOI: 10.1128/AAC.00666-20