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Unravelling the mechanisms of how antibiotics influence growth performance through changes in gut microbiota can lead to the identification of highly productive microbiota in animal production. Here we investigated the effect of zinc bacitracin and avilamycin on growth performance and caecal microbiota in chickens and analysed associations between individual bacteria and growth performance. Two trials were undertaken; each used 96 individually caged 15-day-old Cobb broilers. Trial 1 had a control group ( n =  48) and a zinc bacitracin (50 ppm) treatment group ( n =  48). Trial 2 had a control group ( n =  48) and an avilamycin (15 ppm) treatment group ( n =  48). Chicken growth performance was evaluated over a 10-day period, and caecal microbiota was characterised by sequencing of bacterial 16S rRNA gene amplicons. Avilamycin produced no effect on growth performance and exhibited little significant disturbance of the microbiota structure. However, zinc bacitracin reduced the feed conversion ratio (FCR) in treated birds, changed the composition and increased the diversity of their caecal microbiota by reducing dominant species. Avilamycin only produced minor reductions in the abundance of two microbial taxa, whereas zinc bacitracin produced relatively large shifts in a number of taxa, primarily Lactobacillus species. Also, a number of phylotypes closely related to lactobacilli species were positively or negatively correlated with FCR values, suggesting contrasting effects of Lactobacillus spp. on chicken growth performance. By harnessing such bacteria, it may be possible to develop high-productivity strategies in poultry that rely on the use of probiotics and less on in-feed antibiotics.

Antimicrobials are sometimes given to food animals at low doses in order to promote faster growth. However, the mechanisms by which those drugs improve performance are not fully understood. This study aimed to investigate the impact of zinc bacitracin (55g/ton), enramycin (10g/ton); halquinol® (30g/ton); virginiamycin (16,5g/ton) and avilamycin (10g/ton) on the cecal microbiota of broiler chicken, compared to a control group. Six hundred and twenty four chicks (Cobb 500) arriving to an experimental unit were randomly assigned into each treatment with four repetitions per treatment. The cecal content of 16 animals per treatment (n = 96) was used for DNA extraction and sequencing of the V4 region of the 16S rRNA gene using Illumina technology. The use of antimicrobials induced significant changes in membership but not in structure of the cecal microbiota compared to the control group, suggesting a greater impact on the less abundant species of bacteria present in that environment. Halquinol was the only drug that did not affect microbial membership. Firmicutes comprised the major bacterial phylum present in the cecum of all groups. There was no statistical difference in relative abundances of the main phyla between treated animals and the control group (all P>0.05). Treatment with enramycin was associated with decreased richness and with lower relative abundance of unclassified Firmicutes, Clostridium XI, unclassified Peptostreptococcaceae (all P<0.001) and greater abundance of Clostridium XIVb (P = 0.004) and Anaerosporobacter spp. (P = 0.015), and treatment with bacitracin with greater relative abundance of Bilophila spp. (P = 0.004). Several bacterial genera were identified as representative of usage of each drug. This study used high throughput sequencing to characterize the impact of several antimicrobials in broiler chicken under controlled conditions and add new insights to the current knowledge on how AGPs affect the cecal microbiota of chicken.

Antimicrobial peptides are diverse molecules that include powerful medications such as bacitracin and vancomycin, as well as potent bacterial signaling molecules. Several antimicrobial peptides elicit cell death in gram-positive species by binding to lipid II cycle intermediates and inhibiting the synthesis of peptidoglycan. Many gram-positive organisms have evolved an elegant mechanism to sense and resist such antimicrobial peptides. In these organisms, a “Bce-type” adenosine triphosphate–binding cassette (ABC) transporter forms a protein complex with a two-component system, and together these components sense and provide resistance to antimicrobial peptides present at the cell surface. Conformational switching of Bce-type transporters is proposed to be the stimulus that activates the associated two-component system through a novel flux-sensing mechanism. In this work, we determined the detergent-solubilized structure of the Bce-type ABC transporter BceAB from Bacillus subtilis in two distinct conformational states using cryo–electron microscopy. Together with mass spectrometry and enzymatic data, our structures reveal the overall architecture of the Bce-type transporter family, uncover a specialized lipid-binding pocket for lipid II cycle intermediates, and reveal the conformational changes that are proposed to initiate signaling through the associated two-component system.

The research aimed to evaluate the effects of a commercial blend of phytogenic compounds on the digestibility, antioxidant system, intestinal microbiota, and performance of weaned piglets. Two experiments compared three treatments (diets): control, zinc bacitracin (300 g/t) and blended phytogenic compounds (400 g/t). The first experiment analised of digestibility of the dry matter, organic matter, crude protein, crude energy and metabolizable energy, in addition to blood parameters and gut microbiota in 15 piglets commercial cross-bred, weaned at 28 days of age, castrated males, weighing 9.40 ± 0.622 kg housed in metabolic cages. In the second experiment, performance was evaluated on 108 piglets commercial cross-bred, weaned at 26 days of age, females and castrated males, weighing 7.52 ± 0.356 kg housed in collective stalls with 1,5 m² (3 animals/stall). A completely randomized design was used. The data were subjected to analysis of variance, and the means compared by the Tukey test at 5% significance. There were no differences in piglet digestibility and performance. There was a reduction in the levels of the enzyme superoxide dismutase, lipid peroxidation, and haptoglobulin, and an increase in the levels of the non-protein thiol compound and IgA for the animals receiving the phytogenic compound when compared with the piglets of the other treatments ( p  < 0.05). A tendency in diversity was observed in the intestinal microbiota of piglets receiving the phytogenic compound in the feed ( p  = 0.054). Due to its important role in the antioxidant system and intestinal microbiota, it is suggested that the blend of phytogenic additives can replace antibiotics growth promoters in the diet of newly weaned piglets.

Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet. When compared between antibiotic-supplemented groups, 79 chemicals were altered (43 increased, 36 decreased) in virginiamycin- vs. bacitracin-supplemented chickens. The changes in the levels of intestinal biochemicals provided a distinctive biochemical signature unique to each antibiotic-supplemented group. These biochemical signatures were characterized by increases in the levels of metabolites of amino acids (e.g. 5-hydroxylysine, 2-aminoadipate, 5-hydroxyindoleaceate, 7-hydroxyindole sulfate), fatty acids (e.g. oleate/vaccenate, eicosapentaenoate, 16-hydroxypalmitate, stearate), nucleosides (e.g. inosine, N -methyladenosine), and vitamins (e.g. nicotinamide). These results provide the framework for future studies to identify natural chemical compounds to improve poultry growth performance without the use of in-feed antibiotics.

Bacitracin is a metalloantibiotic agent that is widely used as a medicine and feed additive. It interferes with bacterial cell-wall biosynthesis by binding undecaprenyl-pyrophosphate, a lipid carrier that serves as a critical intermediate in cell wall production. Despite bacitracin’s broad use, the molecular details of its target recognition have not been elucidated. Here we report a crystal structure for the ternary complex of bacitracin A, zinc, and a geranyl-pyrophosphate ligand at a resolution of 1.1 Å. The antibiotic forms a compact structure that completely envelopes the ligand’s pyrophosphate group, together with flanking zinc and sodium ions. The complex adopts a highly amphipathic conformation that offers clues to antibiotic function in the context of bacterial membranes. Bacitracin’s efficient sequestration of its target represents a previously unseen mode for the recognition of lipid pyrophosphates, and suggests new directions for the design of next-generation antimicrobial agents.

Staphylococcus aureus is one of the important pathogens causing human diseases, especially its treatment has great challenges due to its resistance to methicillin and vancomycin. The Bacillus strains are known to be major sources of second metabolites that can function as drugs. Therefore, it is of great value to excavate metabolites with good inhibitory activity against S. aureus from Bacillus strains. In this study, a strain Bacillus paralicheniformis CPL618 with good antagonistic activity against S. aureus was isolated and genome analysis showed that the size was 4,447,938 bp and contained four gene clusters fen, bac, dhb, and lch which are potentially responsible for four cyclic peptides fengycin, bacitracin, bacillibactin, and lichenysin biosynthesis, respectively. These gene clusters were knockout by homologous recombination. The bacteriostatic experiment results showed that the antibacterial activity of ∆bac decreased 72.3% while Δfen, Δdhb, and ΔlchA did not significantly changed as that of wild type. Interestingly, the maximum bacitracin yield was up to 92 U/mL in the LB medium, which was extremely unusual in wild type strains. To further improve the production of bacitracin, transcription regulators abrB and lrp were knocked out, the bacitracin produced by ΔabrB, Δlrp, and ΔabrB + lrp was 124 U/mL, 112 U/mL, and 160 U/ml, respectively. Although no new anti-S. aureus compounds was found by using genome mining in this study, the molecular mechanisms of high yield of bacitracin and anti-S. aureus in B. paralicheniformis CPL618 were clarified. Moreover, B. paralicheniformis CPL618 was further genetically engineered for industrial production of bacitracin.

The cannabinoid cannabidiol (CBD) is characterised in this study as a helper compound against resistant bacteria. CBD potentiates the effect of bacitracin (BAC) against Gram-positive bacteria ( Staphylococcus species, Listeria monocytogenes , and Enterococcus faecalis ) but appears ineffective against Gram-negative bacteria. CBD reduced the MIC value of BAC by at least 64-fold and the combination yielded an FIC index of 0.5 or below in most Gram-positive bacteria tested. Morphological changes in S. aureus as a result of the combination of CBD and BAC included several septa formations during cell division along with membrane irregularities. Analysis of the muropeptide composition of treated S. aureus indicated no changes in the cell wall composition. However, CBD and BAC treated bacteria did show a decreased rate of autolysis. The bacteria further showed a decreased membrane potential upon treatment with CBD; yet, they did not show any further decrease upon combination treatment. Noticeably, expression of a major cell division regulator gene, ezrA , was reduced two-fold upon combination treatment emphasising the impact of the combination on cell division. Based on these observations, the combination of CBD and BAC is suggested to be a putative novel treatment in clinical settings for treatment of infections with antibiotic resistant Gram-positive bacteria.

The threats leading to the extinction of humanity accelerate the evolution and development of materials that are capable of providing conditions for preserving health and, implicitly, life. In our work, we developed drug delivery systems based on mesoporous silica which can deliver an antibiotic, bacitracin, in a more controlled manner. The synthesis of the FDU-12 was performed through a sol–gel method and alternatively functionalized with -NH2 groups or with poly(N-acryloylmorpholine) chains. The loading of bacitracin was performed using the vacuum-assisted method we successfully used to load these mesoporous materials preferentially within the pores as proved by the TGA-DSC results. The release was performed in two types of simulated body fluid (SBF) and this process was evaluated with chromatographic method using UV detection. The obtained data were fitted in three mathematical models of kinetic drug release (Weibull model, Korsmeyer–Peppas model, and nonlinear regression). The antimicrobial evaluation demonstrated that bacitracin-loaded FDU-12 formulations exhibited strong activity against both reference and clinical Staphylococcus strains. At sub-inhibitory concentrations, all formulations significantly reduced microbial adherence and biofilm formation, although certain strain-dependent stimulatory effects were observed. Furthermore, exposure to sub-MIC levels modulated the production of soluble virulence factors (hemolysins, lipase, and amylase), in a formulation- and strain-dependent manner, underscoring the ability of surface-functionalized FDU-12 carriers to influence bacterial pathogenicity while enhancing antimicrobial efficacy.

Background To develop and evaluate Sucrose-Bacitracin agar with 10% sucrose (SB-10), a novel selective medium designed to enhance the isolation and identification of Streptococcus mutans , a key cariogenic pathogen in dental caries. Methods SB-10 was compared to Mitis Salivarius Bacitracin agar with 20% sucrose (MSB-20) for its ability to support S. mutans growth, promote distinctive colony morphology, and differentiate it from other oral bacteria. Sugar particle formation was assessed using wild-type and mutant strains of S. mutans lacking glucosyltransferases B and C (GtfB and GtfC). Liquid chromatography was performed to characterize the sugar particles around colonies. The specificity and clinical utility of SB-10 were further assessed by culturing clinical saliva samples and confirming S. mutans colonies via 16S rRNA sequencing. Results SB-10 supported robust S. mutans growth with larger colonies and distinctive sugar particle formation compared to MSB-20. GtfB and GtfC were essential for sugar particle deposition around colonies. SB-10 demonstrated high specificity by suppressing the growth of non-target oral bacteria and accurately isolating S. mutans from clinical saliva samples, with all colonies confirmed as S. mutans via 16S rRNA sequencing. Conclusions SB-10 is a novel selective medium that enhances the isolation and identification of S. mutans , characterized by unique sugar particles deposition and colony morphology.