-
Frontiers in Veterinary Science 2021Feedlot cattle are usually adapted to high-concentrate diets containing sodium monensin (MON) in more than 14 days. However, for finishing diets with lower energy...
Feedlot cattle are usually adapted to high-concentrate diets containing sodium monensin (MON) in more than 14 days. However, for finishing diets with lower energy content, the use of MON during adaptation may hold dry matter intake (DMI), and virginiamycin (VM) may be an alternative. This study was designed to determine the potential of shortening the adaptation of Nellore cattle to high-concentrate diets using only VM as a sole feed additive relative to feedlot performance, feeding behavior, and ruminal and cecum morphometrics. The experiment was designed as a completely randomized block replicated six times (four animals/pen) in which 120 Nellore bulls (390.4 ± 19.0 kg) were fed in 30 pens for 111 days according to the following treatments: (1) MON and adaptation for 14 days (MON14), (2) MON + VM and adaptation for 14 days (MONVM14), (3) VM and adaptation for 14 days (VM14), (4) VM and adaptation for 9 days (VM9), and (5) VM and adaptation for 6 days (VM6). At the end of the adaptation, 30 animals ( = 1 per pen) were randomly slaughtered for rumen and cecum evaluations. The remaining 90 bulls were harvested at the end of the study. No effects of treatments were observed ( < 0.10) for final body weight, average daily gain (ADG), and hot carcass weight (HCW). Cattle fed VM14 presented a greater ( ≤ 0.03) DMI, expressed as percent of body weight (BW), than animals fed either MON14 or MONVM14; however, cattle fed either MON14 or MONVM14 improved ( ≤ 0.02) the gain-to-feed ratio (G/F) by 10.4 or 8.1%, respectively, when compared to bulls fed VM14. Bulls fed VM14 had smaller ( < 0.05) papillae area (0.34 vs. 0.42 cm) and rumen absorptive surface area (28.9 vs. 33.8 cm) than those fed MON14. The shortening of the adaptation period linearly decreased the 12th rib fat ( = 0.02) and biceps femoris fat daily gain ( = 0.02) of Nellore bulls fed only VM, which linearly decreased the final biceps femoris fat thickness ( < 0.01). Feedlot cattle fed VM as a sole feed additive should not be adapted to high-concentrate diets in less than 14 days. Regardless of either adaptation length or feed additive, feedlot cattle need at least 14 days to adapt to finishing diets.
PubMed: 34409088
DOI: 10.3389/fvets.2021.692705 -
Frontiers in Nutrition 2021() as in-feed probiotics is a potential alternative for antibiotic growth promoters (AGP) in the poultry industry. The current study investigated the effects of on the...
() as in-feed probiotics is a potential alternative for antibiotic growth promoters (AGP) in the poultry industry. The current study investigated the effects of on the performance, immunity, gut microbiota, and intestinal barrier function of broiler chickens. A 42-day feeding trial was conducted with a total of 600 1-day-old Arbor Acres broilers with similar initial body weight, which was randomly divided into one of five dietary treatments: the basal diet (Ctrl), Ctrl + virginiamycin (AGP), Ctrl + A (BSA), Ctrl + B (BSB), and Ctrl + A + B (1:1, BSAB). The results showed significantly increased average daily gain in a step-wise manner from the control, , and to the AGP groups. The mortality rate of the group was significantly lower than the AGP group. The concentrations of serum immunoglobulin (Ig) G (IgG), IgA, and IgM in the and AGP groups were higher than the control group, and the groups had the highest content of serum lysozyme and relative weight of thymus. Dietary increased the relative length of ileum and the relative weight of jejunum compared with the AGP group. The villus height (V), crypt depth (C), V/C, and intestinal wall thickness of the jejunum in the and AGP groups were increased relative to the control group. Dietary increased the messenger RNA (mRNA) expression of ZO-1, Occludin, and Claudin-1, the same as AGP. The contents of lactic acid, succinic acid, and butyric acid in the ileum and cecum were increased by dietary . Dietary significantly increased the and in the ileum and cecum and decreased the and in the cecum. The improved performance and decreased mortality rate observed in the feeding trial could be accrued to the positive effects of on the immune response capacity, gut health, and gut microflora balance, and the combination of two strains showed additional benefits on the intestinal morphology and tight junction protein expressions. Therefore, it can be concluded that dietary A and B could be used as alternatives to synthetic antibiotics in the promotion of gut health and productivity index in broiler production.
PubMed: 34917643
DOI: 10.3389/fnut.2021.786878 -
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 -
Frontiers in Veterinary Science 2020The withdrawal of antibiotic growth promoters from poultry feed has increased the risk of necrotic enteritis (NE) outbreaks. This study examined the effects of a...
The withdrawal of antibiotic growth promoters from poultry feed has increased the risk of necrotic enteritis (NE) outbreaks. This study examined the effects of a probiotic (PROB) or probiotic/prebiotic/essential oil supplement (PPEO) during a subclinical NE challenge. On day (d) of hatch, 960 male broilers were randomized to four groups (8 pens/treatment, 30 birds/pen) including (1) negative control (NC): corn-soybean meal diet; (2) positive control (PC): NC + 20 g Virginiamycin/ton diet; (3) NC + 227 g PROB/ton diet; and (4) NC + 453 g PPEO/ton diet. One d after placement, birds were challenged by a coccidia vaccine to induce NE. Feed intake and body weights were measured on d 8 (NE onset) and end of each feeding period. On d 8, the small intestines of three birds/pen were examined for NE lesions. Jejunum samples and ileal mucosal scrapings from one bird/pen were respectively collected to measure mRNA abundance (d 8 and d 14) and profile the microbiota (d 8 and d 42). Data were analyzed in JMP or QIIME 2 and significance between treatments identified by LSD ( < 0.05). PROB and PPEO had significantly lower mortality (d 0-14) and NE lesion scores compared to NC. Feed conversion ratio was significantly lower in PC, PROB, and PPEO, while average daily gain was higher in PPEO and PC groups compared to NC from d 0-42. On d 8 and d 14, mRNA abundance of claudin-3 was higher in PPEO compared to NC. On d 14, compared to NC, mRNA abundance of sIgA and PGC-1α in PROB and PPEO were lower and higher, respectively. Compared to NC, PPEO increased mTOR abundance on d 14. On d 8, relative abundance of UCG-014, ASF356, and was higher in NC compared to PPEO and PROB, while was lower in NC. had higher abundance in PC compared to PPEO and PROB. Collectively, these data indicate that during a subclinical naturally occurring NE, supplementation of PROB or PPEO supports performance and reduces intestinal lesions, potentially through modifying tight junction proteins, gut microbiota, immune responses, and cell metabolism.
PubMed: 33324697
DOI: 10.3389/fvets.2020.572142 -
Food Additives & Contaminants. Part A,... Sep 2021Cross-contamination of animal feed with antibiotics may occur during manufacturing in feed mills, because shared production lines can be used for medicated and...
Development of a liquid chromatography-tandem mass spectrometry method to determine colistin, bacitracin and virginiamycin M1 at cross-contamination levels in animal feed.
Cross-contamination of animal feed with antibiotics may occur during manufacturing in feed mills, because shared production lines can be used for medicated and non-medicated feed, but may also occur during transport, storage and at the farm level. This is a major issue in the current context where antimicrobial usage must be controlled in order to maintain their effectiveness. A LC-MS/MS method was developed for the determination of colistin, bacitracin A and virginiamycin M1 in feed for pigs, poultry and rabbits at concentrations similar to those encountered in cross-contamination. After investigating various issues related to colistin behaviour and matrix effects, we successfully validated this method according to the requirements of European regulations in terms of linearity, trueness, precision, limit of quantification and limit of decision. Trueness ranged 88.6-107.8% and precision ranged 12.6-21.2%. We then applied this method to the analysis of medicated pig feed to check the performance of the method on "real" samples of medicated feed. We subsequently analysed non-medicated pig, and rabbit feed samples, collected directly on farms, to check the rate of cross-contamination. No samples were contaminated by colistin, bacitracin, or virginiamycin.
Topics: Animal Feed; Animals; Anti-Bacterial Agents; Bacitracin; Chromatography, High Pressure Liquid; Colistin; Food Analysis; Food Contamination; Molecular Conformation; Poultry; Rabbits; Streptogramin A; Swine; Tandem Mass Spectrometry
PubMed: 34043498
DOI: 10.1080/19440049.2021.1922760 -
Animal Nutrition (Zhongguo Xu Mu Shou... Sep 2021The primary aim of this experiment was to critically explore the relationship between the different levels of mixed organic acids (MOA) and growth performance, serum...
The primary aim of this experiment was to critically explore the relationship between the different levels of mixed organic acids (MOA) and growth performance, serum antioxidant status and intestinal health of weaned piglets, as well as to investigate the potential possibility of MOA alternative to antibiotics growth promoters (AGP). A total of 180 healthy piglets (Duroc × [Landrace × Yorkshire]; weighing 7.81 ± 1.51 kg each, weaned at d 28) were randomly divided into 5 treatments: 1) basal diet (CON); 2) CON + chlorinomycin (75 mg/kg) + virginiamycin (15 mg/kg) + guitaromycin (50 mg/kg) (AGP); 3) CON + MOA (3,000 mg/kg) (OA1); 4) CON + MOA (5,000 mg/kg) (OA2); 5) CON + MOA (7,000 mg/kg) (OA3). This study design included 6 replicates per treatment with 6 piglets per pen (barrow:gilt = 1:1) and the experiment was separated into phase 1 (d 1 to 14) and phase 2 (d 15 to 28). In phases 1, 2 and overall, compared with the CON, the feed conversion ratio (FCR) was reduced ( < 0.01) and the average daily gain (ADG) was increased ( < 0.05) in piglets supplemented with AGP, OA1 and OA2. The concentration of serum immunoglobulins G (IgG) was improved ( < 0.05) in piglets supplemented with OA2 in phase 2. In the jejunum and ileum, the villus height:crypt depth ratio was significantly increased ( < 0.01) in piglets fed AGP and OA1. The mRNA expression level of claudin1 and zonula occludens-1 () ( < 0.01) was up-regulated in piglets supplemented with OA1 and OA2. The piglets fed AGP, OA1 and OA2 showed an increase ( < 0.05) in the content of acetate acid and total volatile fatty acids (TVFA) in the cecum, and butyric acid and TVFA in the colon compared with CON. Also, OA1 lowered ( < 0.05) the content of Lachnospiraceae in piglets. These results demonstrated that MOA at 3,000 or 5,000 mg/kg could be an alternative to antibiotics due to the positive effects on performance, immune parameters, and intestinal health of weaned piglets. However, from the results of the quadratic fitting curve, it is inferred that MOA at a dose of 4,000 mg/kg may produce a better effect.
PubMed: 34466678
DOI: 10.1016/j.aninu.2020.11.018 -
Journal of Medical Microbiology Jun 2020The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third...
The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third coronavirus in less than 20 years to cross the species barrier and start spreading by human-to-human transmission. It is the most infectious of the three, currently causing the COVID-19 pandemic. No treatment has been approved for COVID-19. We previously proposed targets that can serve as binding sites for antiviral drugs for multiple coronaviruses, and here we set out to find current drugs that can be repurposed as COVID-19 therapeutics. To identify drugs against COVID-19, we performed an virtual screen with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme for coronavirus replication. Initially, no RdRP structure of SARS-CoV-2 was available. We performed basic sequence and structural analysis to determine if RdRP from SARS-CoV was a suitable replacement. We performed molecular dynamics simulations to generate multiple starting conformations that were used for the virtual screen. During this work, a structure of RdRP from SARS-CoV-2 became available and was also included in the virtual screen. The virtual screen identified several drugs predicted to bind in the conserved RNA tunnel of RdRP, where many of the proposed targets were located. Among these candidates, quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides and suggesting that it has the potential to arrest viral replication by preventing viral RNA synthesis. Quinupristin is an antibiotic that has been in clinical use for two decades and is known to cause relatively minor side effects. Quinupristin represents a potential anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS-CoV-2 but expect that the biomedical community will expeditiously follow up on our findings.
Topics: Animals; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Drug Evaluation, Preclinical; Drug Synergism; Humans; Molecular Conformation; Pandemics; Phylogeny; Pneumonia, Viral; RNA-Dependent RNA Polymerase; Rifampin; SARS-CoV-2; Sequence Alignment; Sequence Analysis, Protein; Virginiamycin; Virus Replication
PubMed: 32469301
DOI: 10.1099/jmm.0.001203 -
Translational Animal Science Jul 2021Two experiments were conducted to evaluate the effects of feed additives [monensin (); 30 mg/kg of dry matter (), and virginiamycin (); 25 mg/kg DM] and grain adaptation...
Two experiments were conducted to evaluate the effects of feed additives [monensin (); 30 mg/kg of dry matter (), and virginiamycin (); 25 mg/kg DM] and grain adaptation programs [adding roughage (; sugarcane bagasse) or not () during the 20-d adaptation period] on performance, carcass characteristics, and nutrient digestibility of cattle fed finishing diets containing 85% whole shelled corn and 15% of a pelleted protein-mineral-vitamin supplement. In Exp.1, 105 Nellore bulls [initial body weight () = 368 ± 25 kg] were used in a complete randomized block design with a 2 × 2 factorial arrangement of treatments, consisting of two feed additives (MON and VM) associated with two adaptation programs (ROU or NO-ROU during the 20-d adaptation period). Effects of feed additives × adaptation programs were not detected ( ≥ 0.13). Feed additives did not affect dry matter intake (), average daily gain (), and feed efficiency () during the 20-d adaptation period ( ≥ 0.35). During the total feeding period (105 d), feeding MON decreased DMI ( ≤ 0.03) compared to VM. Adding sugarcane bagasse to finishing diets during the 20-d adaptation period (ROU) increased ADG ( = 0.05) and G:F ( = 0.03), and tended to increase BW ( = 0.09) compared to NO-ROU. In Exp. 2, 10 ruminally cannulated Nellore steers (BW = 268 ± 38 kg) were used in a completely randomized design to evaluate the effects of the two feed additives used in the Exp. 1 (MON and VM; 5 steers/treatment) on DMI, total apparent digestibility of nutrients, and ruminal fermentation characteristics. No differences in DMI, total tract apparent digestibility of nutrients, and ruminal fermentation characteristics were observed between MON and VM ( ≥ 0.32). An effect of sampling day ( < 0.001) was observed for ruminal pH, which was greater on day 0 compared to day 7, 14, and 21 of the experimental period ( ≤ 0.05). In summary, supplementing monensin and virginiamycin for finishing Nellore bulls fed whole shelled corn diets, resulted in similar growth performance and carcass characteristics. Including sugarcane bagasse to adapt finishing bulls to no-roughage diets containing whole shelled corn is an alternative to increase growth performance.
PubMed: 34671721
DOI: 10.1093/tas/txab119 -
Risk Analysis : An Official Publication... Jun 2020Virginiamycin (VM), a streptogramin antibiotic, has been used to promote healthy growth and treat illnesses in farm animals in the United States and other countries. The...
Virginiamycin (VM), a streptogramin antibiotic, has been used to promote healthy growth and treat illnesses in farm animals in the United States and other countries. The combination streptogramin Quinupristin-Dalfopristin (QD) was approved in the United States in 1999 for treating patients with vancomycin-resistant Enterococcus faecium (VREF) infections. Many chickens and swine test positive for QD-resistant E. faecium, raising concerns that using VM in food animals might select for streptogramin-resistant strains of E. faecium that could compromise QD effectiveness in treating human VREF infections. Such concerns have prompted bans and phase-outs of VM as growth promoters in the United States and Europe. This study quantitatively estimates potential human health risks from QD-resistant VREF infections due to VM use in food animals in China. Plausible conservative (risk-maximizing) quantitative risk estimates are derived for future uses, assuming 100% resistance to linezolid and daptomycin and 100% prescription rate of QD to high-level (VanA) VREF-infected patients. Up to one shortened life every few decades to every few thousand years might occur in China from VM use in animals, although the most likely risk is zero (e.g., if resistance is not transferred from bacteria in food animals to bacteria infecting human patients). Sensitivity and probabilistic uncertainty analyses suggest that this conclusion is robust to several data gaps and uncertainties. Potential future human health risks from VM use in animals in China appear to be small or zero, even if QD is eventually approved for use in human patients.
Topics: Animals; Anti-Bacterial Agents; Chickens; China; Humans; Meat Products; Microbial Sensitivity Tests; Vancomycin-Resistant Enterococci; Virginiamycin
PubMed: 32315459
DOI: 10.1111/risa.13466 -
Frontiers in Nutrition 2021A total of 64 pregnant Bama mini-pigs were used to investigate the effects of maternal probiotic or synbiotic supplementation during gestation and lactation on immune...
A total of 64 pregnant Bama mini-pigs were used to investigate the effects of maternal probiotic or synbiotic supplementation during gestation and lactation on immune response, intestinal morphology, and microbiota community of offspring piglets. The sows were assigned randomly to one of four groups, control group (basal diet), antibiotic group (basal diet supplemented with 50 g/t virginiamycin), probiotic group (basal diet supplemented with 200 mL/d probiotic fermentation broth per pig), or synbiotic group (basal diet supplemented with 200 mL/d probiotic fermentation broth per pig + 500 g/t xylo-oligosaccharides) during pregnancy and lactation periods. After weaning, two piglets close to the average body weight (BW) per litter were selected and fed a basal diet. Eight piglets with similar BW were selected from each group for sample collection at 65 d-old. The results showed that plasma interleukin (IL)-2 and lipopolysaccharide concentrations were decreased ( < 0.05) in the probiotic group, while the immunoglobulin A (IgA) concentration in the probiotic and synbiotic groups was increased ( < 0.05), when compared with the control group. The jejunal IL-10, interferon-α, and secretory IgA (sIgA) concentrations were increased ( < 0.05) in the probiotic and synbiotic groups, as well as the ileal sIgA concentration in the probiotic group. The jejunal villus height (VH) and the ratio of VH to crypt depth were increased ( < 0.05) in the probiotic group, as well as the ileal VH in the synbiotic group. Furthermore, the piglets from the antibiotic group exhibited a lower microbiota diversity in the jejunum and ileum. The piglets from the synbiotic group had higher relative abundances of , and in the jejunum compared with the antibiotic group. Dietary probiotic treatment increased ( < 0.05) the relative abundance of in the ileum compared with the antibiotic and control groups. Spearman's correlation analysis revealed that the relative abundances of , and in the jejunum and in the ileum, were positively correlated with the alterations of immunoglobulin and cytokines. Collectively, these findings suggest that maternal interventions with probiotic or synbiotic are promising strategies for improving the immune response of offspring piglets by altering the gut microbiota.
PubMed: 34307437
DOI: 10.3389/fnut.2021.686053