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Tetrahedron Jun 2019Modular, fully synthetic routes to structurally complex natural products provide useful avenues to access chemical diversity. Herein we report a concise route to...
Modular, fully synthetic routes to structurally complex natural products provide useful avenues to access chemical diversity. Herein we report a concise route to virginiamycin M2, a member of the group A streptogramin class of natural products that inhibits bacterial protein synthesis. Our approach features a longest linear sequence of six steps from 7 simple building blocks, and is the shortest and highest yielding synthesis of any member of the streptogramin class reported to date. We believe this route will enable access to unexplored structural diversity and may serve as a useful tool to improve the therapeutic potential of the streptogramin class of antibiotics.
PubMed: 32764837
DOI: 10.1016/j.tet.2019.04.060 -
Veterinary World Mar 2022Although and are common members of human and animal gut microbiota, their resistance to different antimicrobials makes them important pathogens. Multidrug-resistant...
BACKGROUND AND AIM
Although and are common members of human and animal gut microbiota, their resistance to different antimicrobials makes them important pathogens. Multidrug-resistant enterococci often contaminate foods of animal origin at slaughterhouses. The World Health Organization and the World Organization for Animal Health recommend including animal-derived enterococci in antimicrobial resistance (AMR) monitoring programs. This study aimed to fill a literature gap by determining the current AMR prevalence of and from different food-producing animals in Russia.
MATERIALS AND METHODS
Samples of biomaterial were taken from chickens (n=187), cattle (n=155), pigs (n=49), turkeys (n=34), sheep (n=31), and ducks (n=31) raised at 28 farms in 15 regions of Russia. Isolates of (n=277) and of (n=210) (487 isolates in total; 1 isolate per sample) were tested for resistance to 12 antimicrobials from 11 classes using the broth microdilution method. Three criteria were used for the interpretation of minimum inhibitory concentration: Epidemiological cutoff values (ECOFFs) from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints. The AMR cloud online platform was used for data processing and statistical analysis.
RESULTS
A difference of >10% was found between and resistance to several antimicrobials (erythromycin, gentamycin, tetracycline, chloramphenicol, ciprofloxacin, and streptomycin). In total, resistance to most antimicrobials for enterococci isolates of both species taken from turkeys, chicken, and pigs was higher than cattle, sheep, and ducks. The highest levels were found for turkeys and the lowest for ducks. Among antimicrobials, resistance to bacitracin and virginiamycin was 88-100% in nearly all cases. High levels of clinical resistance were found for both bacteria species: Rifampicin (44-84%) from all animals, tetracycline (45-100%) from poultry and pigs, and erythromycin (60-100%), ciprofloxacin (23-100%), and trimethoprim-sulfamethoxazole (33-53%) from chickens, turkeys, and pigs. No vancomycin-resistant isolates were found. Most isolates were simultaneously resistant to one-three classes of antimicrobials, and they were rarely resistant to more than three antimicrobials or sensitive to all classes.
CONCLUSION
Differences in resistance between enterococci from different farm animals indicate that antimicrobial application is among the crucial factors determining the level of resistance. Conversely, resistance to rifampicin, erythromycin, tetracycline, and ciprofloxacin found in enterococci from farm animals in our study was notably also found in enterococci from wild animals and birds. Our results may be partly explained by the intrinsic resistance of and to some antimicrobials, such as trimethoprim/sulfamethoxazole and bacitracin.
PubMed: 35497972
DOI: 10.14202/vetworld.2022.611-621 -
Asian-Australasian Journal of Animal... Oct 2017This study was determined the influence of virginiamycin supplementation on growth-performance and characteristics of digestion of cattle with decreasing dietary net...
OBJECTIVE
This study was determined the influence of virginiamycin supplementation on growth-performance and characteristics of digestion of cattle with decreasing dietary net energy value of the diet for maintenance (NE) from 2.22 to 2.10 Mcal/kg.
METHODS
Eighty crossbred beef steers (298.2±6.3 kg) were used in a 152-d performance evaluation consisting of a 28-d adaptation period followed by a 124-d growing-finishing period. During the 124-d period steers were fed either a lesser energy dense (LED, 2.10 Mcal/kg NE) or higher energy dense (HED, 2.22 Mcal/kg NE) diet. Diets were fed with or without 28 mg/kg (dry matter [DM] basis) virginiamycin in a 2×2 factorial arrangement. Four Holstein steers (170.4±5.6 kg) with cannulas in the rumen (3.8 cm internal diameter) and proximal duodenum were used in 4×4 Latin square experiment to study treatment effects on characteristics of digestion.
RESULTS
Neither diet energy density nor virginiamycin affected average daily gain (p>0.10). As expected, dry matter intake and gain efficiency were greater (p<0.01) for LED- than for HED-fed steers. Virginiamycin did not affect estimated net energy value of the LED diet. Virginiamycin increased estimated NE of the HED diet. During daylight hours when the temperature humidity index averaged 81.3±2.7, virginiamycin decreased (p<0.05) ruminal temperature. Virginiamycin did not influence (p>0.10) ruminal or total tract digestion. Ruminal (p = 0.02) and total tract digestion (p<0.01) of organic matter, and digestible energy (p<0.01) were greater for HED vs LED. Ruminal microbial efficiency was lower (p<0.01) for HED vs LED diets.
CONCLUSION
The positive effect of virginiamycin on growth performance of cattle is due to increased efficiency of energy utilization, as effects of virginiamycin on characteristics of digestion were not appreciable. Under conditions of high ambient temperature virginiamycin may reduce body temperature.
PubMed: 28335092
DOI: 10.5713/ajas.16.0826 -
MSystems Aug 2021The antibiotic growth promoters (AGPs) flavophospholipol and virginiamycin have been widely used for decades in food animal production. AGP activity is believed to be...
The antibiotic growth promoters (AGPs) flavophospholipol and virginiamycin have been widely used for decades in food animal production. AGP activity is believed to be partly modulated by gut microbial composition although exact AGP-induced changes remain unclear. In a controlled intervention study, we studied the effect of flavophospholipol and virginiamycin on the broiler chicken ileal microbiota spanning from birth to 39 days. Using 16S rRNA gene profiling and prediction of metabolic activity, we show that both AGPs result in dynamic microbial shifts that potentially increase anti-inflammatory mechanisms and bioavailability of several essential nutrients by decreasing degradation (flavophospholipol) or increasing biosynthesis (virginiamycin). Further, virginiamycin-supplemented broilers showed increased colonization with potentially pathogenic bacteria, Clostridium perfringens, Campylobacter, and Escherichia/ spp. Overall, we show that both AGPs induce microbial changes potentially beneficial for growth. However, the increase in (foodborne) pathogens shown here with virginiamycin use could impact not only broiler mortality but also human health. Antibiotic growth promoters (AGPs) are commonly used within poultry farming to increase muscle growth. Microbial composition in the gut is known to be influenced by AGP use although exact AGP-induced changes remain unclear. Utilizing 16S rRNA gene profiling, this study provides a first head-to-head comparison of the effect of the two most commonly used AGPs, flavophospholipol and virginiamycin, on the broiler chicken ileum microbiota over time. We found that supplementation with both AGPs altered ileal microbial composition, thereby increasing potential bioavailability of essential nutrients and weight gain. Flavophospholipol showed a slight benefit over virginiamycin as the latter resulted in more extensive microbial perturbations including increased colonization by enteropathogens, which could impact broiler mortality.
PubMed: 34463581
DOI: 10.1128/mSystems.00381-21 -
Gut Pathogens Dec 2023In this study, four antimicrobial growth promoters, including virginiamycin, josamycin, flavophospholipol, poly 2-propenal 2-propenoic acid and ultraviolet light, were...
In this study, four antimicrobial growth promoters, including virginiamycin, josamycin, flavophospholipol, poly 2-propenal 2-propenoic acid and ultraviolet light, were tested for their capacity to induce stx-bacteriophages in 47 Shiga toxin-producing E. coli O157:H7 isolates. Induced bacteriophages were characterized for shiga toxin subtypes and structural genes by PCR, DNA restriction fragment length polymorphisms (RFLP) and morphological features by electron microscopy. Bacteriophages were induced from 72.3% (34/47) of the STEC O157:H7 isolates tested. Bacteriophage induction rates per induction method were as follows: ultraviolet light, 53.2% (25/47); poly 2-propenal 2-propenoic acid, 42.6% (20/47); virginiamycin, 34.0% (16/47); josamycin, 34.0% (16/47); and flavophospholipol, 29.8% (14/47). A total of 98 bacteriophages were isolated, but only 59 were digestible by NdeI, revealing 40 RFLP profiles which could be subdivided in 12 phylogenetic subgroups. Among the 98 bacteriophages, stx2a, stx2c and stx2d were present in 85.7%, 94.9% and 36.7% of bacteriophages, respectively. The Q, P, CIII, N1, N2 and IS1203 genes were found in 96.9%, 82.7%, 69.4%, 40.8%, 60.2% and 73.5% of the samples, respectively. Electron microscopy revealed four main representative morphologies which included three bacteriophages which all had long tails but different head morphologies: long hexagonal head, oval/oblong head and oval/circular head, and one bacteriophage with an icosahedral/hexagonal head with a short thick contractile tail. This study demonstrated that virginiamycin, josamycin, flavophospholipol and poly 2-propenal 2-propenoic acid induce genetically and morphologically diverse free stx-converting bacteriophages from STEC O157:H7. The possibility that these antimicrobial growth promoters may induce bacteriophages in vivo in animals and human hosts is a public health concern. Policies aimed at minimizing or banning the use of antimicrobial growth promoters should be promoted and implemented in countries where these compounds are still in use in animal agriculture.
PubMed: 38057920
DOI: 10.1186/s13099-023-00590-9 -
PloS One 2022This study aimed to compare the effects of different levels of cashew nutshell liquid (CNSL) and castor oil (CNSL-castor oil) with growth-promoting antibiotics...
This study aimed to compare the effects of different levels of cashew nutshell liquid (CNSL) and castor oil (CNSL-castor oil) with growth-promoting antibiotics associated with anticoccidials in broiler chickens challenged with coccidiosis. In this work, 2520 one-day-old male broiler chicks (Cobb) were randomly assigned to 84 pens, containing 30 birds each. The experimental design was completely randomized, with seven treatments: enramycin (8 ppm), virginiamycin (16.5 ppm), and tylosin (55 ppm); different doses of CNSL-castor oil (0.5, 0.75, and 1.00 kg/t); and a control diet (without additives). All treatments received semduramicin + nicarbazin (500 g/t; Aviax® Plus) from 0 to 28 d and monensin sodium (100 ppm; Elanco) from 29 to 35 days of age, when the feed was without antibiotics. The challenge was introduced at 14 days of age by inoculating broiler chickens with sporulated Eimeria tenella, Eimeria acervulina, and Eimeria maxima oocysts via oral gavage. In addition to performance parameters, intestinal contents were collected at 28 and 42 days of age for microbiota analysis by sequencing the 16s rRNA in V3 and V4 regions using the Illumina MiSeq platform. Taxonomy was assigned using the SILVA database (v. 138) with QIIME2 software (v. 2020.11). After one week of challenge, the broilers that received tylosin had a higher body weight gain (BWG) than those in the control group (p < 0.05), while the other treatments presented intermediate values. At 28 d, the BWG was lower for the control, CNSL-Castor oil 0.5 kg/t, enramycin, and virginiamycin treatments than that in the tylosin treatment. The inclusion of CNSL-Castor oil at concentrations of 0.75 and 1 kg/t acted as an intermediate treatment (p < 0.05). For alpha diversity, using the Shannon index, it was possible to observe the effect of age, with substantial diversity at 42 d. The Firmicutes phylum had the highest abundance, with values between 84.33% and 95.16% at 42 d. Tylosin showed better performance indices than other treatments. CNSL-castor oil treatments with concentrations of 0.75 and 1 kg/t showed similar results to those of enramycin and virginiamycin. Furthermore, CNSL-castor oil acted as a modulator of intestinal microbiota, reducing the abundance of pathogenic bacteria.
Topics: Anacardium; Animals; Anti-Bacterial Agents; Castor Oil; Chickens; Coccidiosis; Eimeria; Male; Microbiota; RNA, Ribosomal, 16S; Tylosin; Virginiamycin
PubMed: 35793288
DOI: 10.1371/journal.pone.0270350 -
Animal Nutrition (Zhongguo Xu Mu Shou... Dec 2018The gut microbiota plays important roles in animal overall health and productiveness. Balancing host gut microbiota by probiotics has been documented. Our previous study...
The gut microbiota plays important roles in animal overall health and productiveness. Balancing host gut microbiota by probiotics has been documented. Our previous study showed that () and B10 () significantly improve growth performance and modulate the intestinal histomorphology in broilers. To increase the knowledge regarding and , this study investigated the effects of these 2 probiotic strains on the gut microbiota in broilers. Three hundred 1-day-old Sanhuang broilers (Chinese cross breed) were randomly divided into 3 groups, each group with 5 replications ( = 20). The control group (CK) was fed a basal diet containing an antibiotic (virginiamycin, 20 mg/kg) and the other 2 groups received and (1 × 10 cfu/kg of feed) in addition to the basal diet. After 72 d of treatment, pyrosequencing revealed that the bacterial communities varied along the section of intestinal tract in the control and groups, but not in the group. No difference in microbial diversity was observed among 3 groups. The major phyla observed along the GI tract of broilers (particularly in the duodenum and cecum) were Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia, which were considered potentially growth performance-related. Bacteroidetes, Proteobacteria, and Verrucomicrobia were observed at a much higher abundance in the jejunums and ileums of the group ( < 0.05). In addition, the jejunal microbial communities formed 3 different clusters at either the genus level or the category of metabolism among the groups, based on the principal component analyses. These data indicated that and can modulate the microbial ecosystem, and subsequently enhance the health status of broilers.
PubMed: 30564755
DOI: 10.1016/j.aninu.2018.03.004 -
Accounts of Chemical Research Apr 2021Continued, rapid development of antimicrobial resistance has become worldwide health crisis and a burden on the global economy. Decisive and comprehensive action is...
Continued, rapid development of antimicrobial resistance has become worldwide health crisis and a burden on the global economy. Decisive and comprehensive action is required to slow down the spread of antibiotic resistance, including increased investment in antibiotic discovery, sustainable policies that provide returns on investment for newly launched antibiotics, and public education to reduce the overusage of antibiotics, especially in livestock and agriculture. Without significant changes in the current antibiotic pipeline, we are in danger of entering a post-antibiotic era.In this Account, we summarize our recent efforts to develop next-generation streptogramin and lankacidin antibiotics that overcome bacterial resistance by means of modular chemical synthesis. First, we describe our highly modular, scalable route to four natural group A streptogramins antibiotics in 6-8 steps from seven simple chemical building blocks. We next describe the application of this route to the synthesis of a novel library of streptogramin antibiotics informed by in vitro and in vivo biological evaluation and high-resolution cryo-electron microscopy. One lead compound showed excellent inhibitory activity in vitro and in vivo against a longstanding streptogramin-resistance mechanism, virginiamycin acetyltransferase. 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.Second, we recount our modular approaches toward lankacidin antibiotics. Lankacidins are a group of polyketide natural products with activity against several strains of Gram-positive bacteria but have not been deployed as therapeutics due to their chemical instability. We describe a route to several diastereomers of 2,18--lankacidinol B in a linear sequence of ≤8 steps from simple building blocks, resulting in a revision of the C4 stereochemistry. We next detail our modular synthesis of several diastereoisomers of -lankacidinol that resulted in the structural reassignment of this natural product. These structural revisions raise interesting questions about the biosynthetic origin of lankacidins, all of which possessed uniform stereochemistry prior to these findings. Finally, we summarize the ability of several - and -lankacidins to inhibit the growth of bacteria and to inhibit translation in vitro, providing important insights into structure-function relationships for the class.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Gram-Negative Bacteria; Gram-Positive Bacteria; Macrolides; Microbial Sensitivity Tests; Molecular Conformation; Molecular Dynamics Simulation; Ribosomes; Streptogramins; Virginiamycin
PubMed: 33792282
DOI: 10.1021/acs.accounts.0c00894 -
Microorganisms Sep 2021Mature and stable intestinal microbiota in chickens is essential for health and production. Slow development of microbiota in young chickens prolongs the precarious...
Mature and stable intestinal microbiota in chickens is essential for health and production. Slow development of microbiota in young chickens prolongs the precarious period before reaching mature configuration. Whether probiotics can play a role in the early maturation of intestinal microbiota is unknown. To address this, day-old chicks were assigned into six groups: NC (basal diet), PC (virginiamycin), low (BPL) and high-dose (BPH) of and low (BSL) and high-dose (BSH) of . Cecal contents at days 7, 14, 28 and 42 were used to analyze the treatment and time effects on the diversity and composition of microbiota. Overall, the alpha diversity was significantly decreased in the NC group between days 7 and 14, while this decline was prevented in the probiotic (BSL and BSH) and even reversed in the BPH group. The beta-diversity showed significant responses of microbial communities to probiotics in first two weeks of life. Analyses of the abundance of microbiota reflected that members of the family Ruminococcaceae (, , , and ), which were dominant in mature microbiota, were significantly higher in abundance at day 14 in the probiotic groups. Conversely, the abundance of genera within the family Lachnospiraceae (, and ) was dominant in early dynamic microbiota but was significantly lower in the probiotic groups at day 14. The and abundance was higher, while the Enterobacteriaceae abundance was lower in the probiotic groups. In summary, the probiotics efficiently helped the cecal microbiota reach mature configuration earlier in life. These results could be used for the future manipulation of microbiota from the perspective of improving poultry performance.
PubMed: 34576794
DOI: 10.3390/microorganisms9091899 -
Frontiers in Veterinary Science 2022This study evaluated the effects of maternal probiotics and synbiotics addition on several traits and parameters in offspring. A total of 64 Bama mini pigs were randomly...
Probiotics and Synbiotics Addition to Bama Mini-Pigs' Diet Improve Carcass Traits and Meat Quality by Altering Plasma Metabolites and Related Gene Expression of Offspring.
This study evaluated the effects of maternal probiotics and synbiotics addition on several traits and parameters in offspring. A total of 64 Bama mini pigs were randomly allocated into the control (basal diet), antibiotic (50 g/t virginiamycin), probiotics (200 mL/day probiotics), or synbiotics (500 g/t xylo-oligosaccharides and 200 mL/day probiotics) group and fed with experimental diets during pregnancy and lactation. After weaning, two piglets per litter and eight piglets per group were selected and fed with a basal diet. Eight pigs per group were selected for analysis at 65, 95, and 125 days of age. The results showed that the addition of probiotics increased the average daily feed intake of the pigs during the 66- to 95-day-old periods and backfat thickness at 65 and 125 days of age, and that the addition of synbiotics increased backfat thickness and decreased muscle percentage and loin-eye area at 125 days of age. The addition of maternal probiotics increased the cooking yield and pH value at 65 and 95 days of age, respectively, the addition of synbiotics increased the meat color at 95 days of age, and the addition of probiotics and synbiotics decreased drip loss and shear force in 65- and 125-day-old pigs, respectively. However, maternal antibiotic addition increased shear force in 125-day-old pigs. Dietary probiotics and synbiotics addition in sows' diets increased several amino acids (AAs), including total AAs, histidine, methionine, asparagine, arginine, and leucine, and decreased glycine, proline, isoleucine, α-aminoadipic acid, α-amino-n-butyric acid, β-alanine, and γ-amino-n-butyric acid in the plasma and (LT) muscle of offspring at different stages. In the LT muscle fatty acid (FA) analysis, saturated FA (including C16:0, C17:0, and C20:0) and C18:1n9t contents were lower, and C18:2n6c, C16:1, C20:1, and unsaturated FA contents were higher in the probiotics group. C10:0, C12:0, and C14:0 contents were higher in 65-day-old pigs, and C20:1 and C18:1n9t contents were lower in the synbiotics group in 95- and 125-day-old pigs, respectively. The plasma biochemical analysis revealed that the addition of maternal probiotics and synbiotics decreased plasma cholinesterase, urea nitrogen, and glucose levels in 95-day-old pigs, and that the addition of synbiotics increased plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol concentrations in 65-day-old pigs and triglyceride concentration in 125-day-old pigs. The addition of maternal probiotics and synbiotics regulated muscle fiber type, myogenic regulation, and lipid metabolism-related gene expression of LT muscle in offspring. In conclusion, the addition of maternal probiotics and synbiotics improved the piglet feed intake and altered the meat quality parameters, plasma metabolites, and gene expression related to meat quality.
PubMed: 35873696
DOI: 10.3389/fvets.2022.779745