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Bacitracin is a macrocyclic peptide antibiotic that is widely used as a topical treatment for infections caused by gram-positive bacteria. Mechanistically, bacitracin targets bacteria by specifically binding to the phospholipid undecaprenyl pyrophosphate (C55PP), which plays a key role in the bacterial lipid II cycle. Recent crystallographic studies have shown that when bound to C55PP, bacitracin adopts a highly ordered amphipathic conformation. In doing so, all hydrophobic side chains align on one face of the bacitracin-C55PP complex, presumably interacting with the bacterial cell membrane. These insights led us to undertake structure-activity investigations into the individual contribution of the nonpolar amino acids found in bacitracin. To achieve this we designed, synthesized, and evaluated a series of bacitracin analogues, a number of which were found to exhibit significantly enhanced antibacterial activity against clinically relevant, drug-resistant pathogens. As for the natural product, these next-generation bacitracins were found to form stable complexes with C55PP. The structure-activity insights thus obtained serve to inform the design of C55PP-targeting antibiotics, a key and underexploited antibacterial strategy. [ABSTRACT FROM AUTHOR]

The food enzyme subtilisin (EC 3.4.21.62) is produced with the non‐genetically modified Bacillus paralicheniformis strain AP‐01 by Nagase (Europa) GmbH. It was considered free from viable cells of the production organism. The food enzyme is intended to be used in five food manufacturing processes. Since residual amounts of food enzyme‐total organic solids (TOS) are removed in one process, dietary exposure was calculated only for the remaining four food manufacturing processes. It was estimated to be up to 0.875 mg TOS/kg body weight per day in European populations. The production strain of the food enzyme has the capacity to produce bacitracin and thus failed to meet the requirements of the Qualified Presumption of Safety approach. Bacitracin was detected in the industrial fermentation medium but not in the food enzyme itself. However, the limit of detection of the analytical method used for bacitracin was not sufficient to exclude the possible presence of bacitracin at a level representing a risk for the development of antimicrobial resistant bacteria. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and twenty‐eight matches with respiratory allergens, one match with a contact allergen and two matches with food allergens (melon and pomegranate) were found. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme, particularly in individuals sensitised to melon or pomegranate, cannot be excluded, but would not exceed the risk of consuming melon or pomegranate. Based on the data provided, the Panel could not exclude the presence of bacitracin, a medically important antimicrobial, and consequently the safety of this food enzyme could not be established. [ABSTRACT FROM AUTHOR]

Background The extensive clinical use of Fluoroquinolones (FQs) led to the development of bacterial resistance against these agents. In this work, new lipophilic FQs were designed, prepared and screened against standard and resistant bacteria. A series of novel 7-substituted anilino-8-nitroFQ acids 3 (a-e), their reduced derivatives 4 (a-e) and their triazolo 5 (a-c) were successfully prepared, identified and characterized using NMR, and MS. FQs 3-5(a-e) were then evaluated for the in vitro antibacterial activity against standard and resistant gram-positive and gram-negative strains using serial dilution method. Combination between the new FQs and different classes of antibiotics were also tested for possible synergistic effect using checkerboard technique. Results The outcomes of the new FQs showed comparable and superior activity against both the standard strains S.aureus and E.coli with remarkable activity against the standard S.aureus strain. The reduced series 4 were the most active group among all derivatives with nanogram concentrations for 4d (60 ng/mL) and 4e (15 ng/mL) against the standard gram positive strain. Our compounds revealed appreciable or comparable MIC mean values to standard against resistant gram-positive strains (MRSA) with no inhibitory activity against gram-negative strains (MDR E.coli). The hydroxyl derivatives 6 have showed the strongest MIC mean values among all compounds. Combination of these compounds with bacitracin, ampicillin and cephalexin showed synergistic effect with fractional inhibitory concentration (FIC) index between 0.185-0.375. While combinations with erythromycin, neomycin and tetracycline showed indifference effect with FIC index 2. Conclusions Evidently increasing number of hydrogen bond acceptor/donor leads to significant increase in activity presented by compounds 4e and 6e. These findings would open the floor for these novel antibacterial agents to be used alone or in combinations with conventional antibiotics for treatment of pathogenic bacteria. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the effect of adding Spirulina platensis to replace zinc bacitracin on performance, egg quality, blood profile, total gut bacteria, and liver histopathology of local indigenous Arab chicken (Gallus turcicus). One hundred and eight 28-week-old laying hens were distributed randomly to three treatments: T0 (control diet), T1 (T0 + 1% S. platensis), and T2 (T0 + 0.04% zinc bacitracin). The treatment was applied for 49 days. S. platensis and zinc bacitracin decreased feed intake (p<0.05), but the egg mass had no significant effect; this provides a good improvement in feed conversion ratio (p<0.05). S. platensis helped maintain persistent egg production (p<0.05). S. platensis and zinc bacitracin provided the best results on haugh unit (p<0.05). S. platensis increased the yolk score (p<0.05). Zinc bacitracin decreased erythrocytes (p<0.05) but was not significantly different from S. platensis. S. platensis and zinc bacitracin increased mean corpuscular volume (MCV) (p<0.05). Blood chemical profile and total gut bacteria were not affected by the treatments. S. platensis was the best at maintaining liver's health (p<0.05). This research concludes that S. platensis can efficiently optimize feed consumption, enhance performance, maintain egg quality, and protect the liver damage of Arab chicken. Therefore, S. platensis could be considered to replace the use of antibiotics. [ABSTRACT FROM AUTHOR]

Enterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope‐acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two‐component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. To better understand the regulation of DAP resistance and how this relates to mutations observed in DAP‐resistant clinical isolates of enterococci, we here explored the interplay between these two regulatory pathways. Our results show that SapR regulates an additional resistance operon, dltXABCD, a known DAP resistance determinant, and show that LiaFSR regulates the expression of sapRS. This regulatory structure places SapRS‐target genes under dual control, where expression is directly controlled by SapRS, which itself is up‐regulated through LiaFSR. The network structure described here shows how Enterococcus faecalis coordinates its response to cell envelope attack and can explain why clinical DAP resistance often emerges via mutations in regulatory components. [ABSTRACT FROM AUTHOR]

Campylobacter hepaticus, the causative agent of Spotty Liver Disease (SLD) is an important disease in cage-free egg producing chickens causing mortality and production drops. C. hepaticus is a slow growing Campylobacter easily overgrown by fecal bacteria. It is currently only reliably isolatable from bile samples. A selective media for isolation from feces or environment would assist diagnosis and impact assessment. Growth of five Australian C. hepaticus isolates was studied using Horse blood agar (HBA), sheep blood agar (SBA), Bolton, Preston and Brain Heart Infusion (BHI) base media. Blood and/or bile were added to Bolton, Preston and BHI medias. C. jejuni was used as a positive control. Plates were incubated in duplicate under microaerophilic conditions at 42°C for 10 days and examined at days 3–5 and 7–10 of incubation. Each isolate was examined for sensitivity to 14 antimicrobials using HBA sensitivity plates. Growth was inhibited by BHI and by added bile, while blood improved growth. Further replicates using SBA, HBA, Bolton and Preston media showed best growth on Bolton agar with blood. All five C. hepaticus isolates were resistant to trimethoprim and vancomycin, while four were also resistant to rifampicin and bacitracin. Media based upon Bolton plus blood supplemented with vancomycin and trimethoprim might be used as the most appropriate media for selective growth of C. hepaticus. The addition of bile to media for C. hepaticus isolation and growth will inhibit growth and is not advised. [ABSTRACT FROM AUTHOR]

Bacitracin Methylene Disalicylate (BMD), as a feed additive to poultry diets, enhances digestion, prevents Salmonella enteritidis (SE) colonization, and treats current infections. The objective of this study was to utilize a quantitative proteomic approach to determine the effect of BMD feed additive on broiler chickens challenged with SE in the spleen proteome. At 1 d of age, chicks were randomly allocated into four groups: control with and without SE challenge (CON, n = 60; CON-SE, n = 60), BMD with and without SE challenge (BMD, n = 60; BMD-SE, n = 60). Birds in the CON-SE and BMD-SE treatment were administered SE inoculum by oral gavage. On day three and day seven post-gavage, the spleen was collected aseptically from birds in each treatment group (CON, n = 4/day; CON-SE, n = 4/day; BMD, n = 4/day; BMD-SE, n = 4/day). Proteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed an increased abundance of 115 proteins and decreased of 77 due to the BMD. Proteins that decreased in abundance were enriched for fibrinogen complex and extracellular space, whereas proteins that increased in abundance were enriched for proteasome-mediated ubiquitin-dependent protein catabolic process and mitochondrion. Analysis of the interaction between BMD and the Salmonella challenge found 230 differentially abundant proteins including proteins associated with RNA binding, spliceosome, protein transport, and cell adhesion among the upregulated proteins, and those associated with protein folding, carbon metabolism, biosynthesis of nucleotide sugars, response to oxidative stress, positive regulation of NIK/NF-kappaB signaling, and inflammatory response among the downregulated proteins. The impact of BMD treatment on spleen proteome indicates an anti-apoptotic effect. BMD also modified the response of the spleen to the SE challenge with a marked decrease in proteins that prompt cytokine synthesis and an increase in proteins involved in the selective removal of unfolded proteins. [ABSTRACT FROM AUTHOR]

Context. Currently, since the use of antibiotics as growth promoters in animals has been banned worldwide, it is necessary to use other additives that indorse an adequate balance of the intestinal microbiota, so as to render better results in nutrient acquisition and health of poultry, yielding adequate growth and performance. Aim. The study evaluated the effects of dietary supplementation with symbiotics during the grower phase, to replace bacitracin zinc. Methods. The experiment included a total of 684 pullets of the Dekalb White strain, from 6 to 15 weeks of age, distributed in a completely randomised design, with five treatments, and eight replications of 18 birds each. The treatments were composed of two base diets, namely one of corn and soybean meal (reference diet, RD), and another of meat and bone meal (MBM), in addition to two more diets based on MBM, one with an addition of 0.05% of bacitracin zinc (Bac Zn), and the other with 0.1% of symbiotic provided to two groups, including one group that had already consumed the symbiotic since the first day of life (starter phase, Symb-S), and the other that started to consume at the beginning of the experiment (grower phase, Symb-G). Performance, blood variables, nutrient metabolisability, weights of organs of the immune and digestive system, and measurement of length (intestine and caecum) were determined. Data were compared using orthogonal contrast. Key results. The birds fed with the RD diet presented a worse overall performance and coefficients of apparent metabolisability of dry matter (CAMDM) (6-10 weeks) than did those fed the MBM diet. Birds fed with the Bac Zn diet showed better bodyweight gain (6-15 weeks), coefficients of apparent metabolisability of gross energy (CAMGE) and CAMDM (6-10 weeks) than did those fed the MBM diet. Birds fed with symbiotic diets had better responses in blood biochemistry variables (alkaline phosphatase, total proteins) than did those fed the Bac Zn diet. Conclusion. The use of symbiotics since the starter and grower phase can replace the use of Bac Zn, without affecting the biochemical and metabolic responses of the pullets. Implications. Symbiotics improved utilisation of diet nutrients, maintenance of physiological homeostasis, and growth of pullets. [ABSTRACT FROM AUTHOR]

Swine dysentery, caused by Brachyspira hyodysenteriae and the newly recognized Brachyspira hampsonii in grower-finisher pigs, is a substantial economic burden in many swine-rearing countries. Antimicrobial therapy is the only commercially available measure to control and prevent Brachyspira -related colitis. However, data on antimicrobial susceptibility trends and genetic diversity of Brachyspira species from North America is limited. We evaluated the antimicrobial susceptibility profiles of U.S. Brachyspira isolates recovered between 2013 and 2022 to tiamulin, tylvalosin, lincomycin, doxycycline, bacitracin, and tylosin. In addition, we performed multilocus sequence typing (MLST) on 64 B. hyodysenteriae isolates. Overall, no distinct alterations in the susceptibility patterns over time were observed among Brachyspira species. However, resistance to the commonly used antimicrobials was seen sporadically with a higher resistance frequency to tylosin compared to other tested drugs. B. hampsonii was more susceptible to the tested drugs than B. hyodysenteriae and B. pilosicoli. MLST revealed 16 different sequence types (STs) among the 64 B. hyodysenteriae isolates tested, of which 5 STs were previously known, whereas 11 were novel. Most isolates belonged to the known STs: ST93 (n = 32) and ST107 (n = 13). Our findings indicate an overall low prevalence of resistance to clinically important antimicrobials other than tylosin and bacitracin, and high genetic diversity among the clinical Brachyspira isolates from pigs in the United States during the past decade. Further molecular, epidemiologic, and surveillance studies are needed to better understand the infection dynamics of Brachyspira on swine farms and to help develop effective control measures. [ABSTRACT FROM AUTHOR]

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Background: In cariology studies, mitis-salivariusbacitracin (MSB) agar has been commonly considered as the selective medium for Streptococcus mutans growth. The present study was the part of a funded project (a noninferiority randomized controlled trial) which compared the efficacy of a plant extract-based mouth rinse with that of a fluoride mouth rinse on the S. mutans counts of the children. Aim: This study aimed to identify the frequency of detection of S. mutans and nonstreptococcal bacterial species from the dental plaque of caries active children using a combined technique of anaerobic culture and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Settings and Methods: Caries-active children (8-12 years old) were enrolled from a pediatric dental outpatient department at a tertiary care hospital. From each participant, dental plaque samples were collected from carious surfaces under sterilized conditions and then subjected to anaerobic culture. After 48 h of incubation, the bacterial colonies were isolated by sub-culture and identified by the MALDI-TOF. Results: In all, 13 different bacterial species were isolated from the MSB agar medium. Other than S. mutans species, colonies of bacterial species such as Veillonella dispar, Streptococcus anginosus, Veillonella parvula, and Streptococcus gordonii were also frequently observed from the medium. Conclusions: The study concluded that several bacterial strains, both streptococcal and nonstreptococcal, could be isolated from the MSB agar medium; hence, this medium should no longer be considered selective medium for the culture of S. mutans in clinical and epidemiological studies. [ABSTRACT FROM AUTHOR]

Bacitracin is an antimicrobial used in the feed or water of poultry in the U.S. for the prevention, treatment, and control of clostridial diseases such as necrotic enteritis. Concern has been raised that bacitracin can select for antimicrobial-resistant bacteria that can be transmitted to humans and subsequently cause disease that is more difficult to treat because of the resistance. The objective of the present study was to perform a quantitative risk assessment (QRA) to estimate the potential risk in the U.S. of human infection with antimicrobial-resistant Enterococcus faecalis and E. faecium derived from chicken and turkey products as a result of bacitracin usage in U.S. poultry. The modeling approach estimated the annual number of healthcare-associated enterococcal infections in the U.S. that would be resistant to antimicrobial therapy and that would be derived from poultry sources because of bacitracin use in poultry. Parameter estimates were developed to be “maximum risk” to overestimate the risk to humans. While approximately 60% of E. faecalis and E. faecium derived from poultry were predicted to possess bacitracin resistance based on the presence of the bcrABDR gene locus, very few human-derived isolates possessed this trait. Furthermore, no vancomycin or linezolid-resistant strains of E. faecalis or E. faecium were detected in poultry sources between the years 2002 and 2019. The model estimated the number of antimicrobial-resistant E. faecalis and E. faecium cases per year that might resist therapy due to bacitracin use in poultry as 0.86 and 0.14, respectively, which translates to an annual risk estimate for E. faecalis of less than 1 in 350 million and for E. faecium of less than 1 in 2 billion for members of the U.S. population. Even with the use of risk-maximizing assumptions, the results indicate that there is a high probability that the use of bacitracin according to label instructions in U.S. poultry presents a negligible risk to human health.

Mathematical modeling aims to simplify the complex process of drug release and to gain knowledge about the release mechanisms specific to a given material system. Consequently, a mathematical model focuses primarily on one or two important factors. Drug release aims to maximize the bioactivity of both naturally derived and synthetically derived macromolecules, thus increasing their clinical applicability and improving the overall quality of life. This study focused on fabricating PLA composites with different weight percentages of Bacitracin Zinc (0.5, 1.0, and 2.0) and evaluating their potential as a drug delivery system. To understand the release mechanism of Bacitracin Zinc from the PLA composites, we developed a Franz diffusion kinetic model and a mathematical model for cumulative release kinetics. The Franz diffusion model was utilized to analyze the release behavior of the PLA/Bacitracin Zinc composite structure. The results indicated a sustained release rate, following a Zero Order release kinetics pattern. Furthermore, the shelf life of the composite structure was determined to be 125 days. Python programming was employed to model the release behavior and estimate the shelf life of Bacitracin Zinc (0.5, 1.0, and 2.0) incorporated into the PLA matrix to compare different weight percentages' behavior and shelf life. [ABSTRACT FROM AUTHOR]

A novel probe for bacteria was simply synthesized through the solvent-induced co-assembly of bacitracin (AMP) and thymolphthalein (TP) without complicated modification. Combining with aptamer–Fe3O4, AMP/TP nanoparticles were used for the colorimetric detection of Escherichia coli with good sensitivity through the NaOH-triggered blue color and a smartphone-based App. [ABSTRACT FROM AUTHOR]

This study was designed to identify Enterococcus faecalis from clinical mastitis of cattle and determine their antimicrobial resistance and virulence determinants to evaluate their potential public health significance. A total of 105 composite milk samples (80 from cattle with clinical mastitis and 25 from apparently healthy cattle) were analyzed. E. faecalis were isolated by culturing on enterococcal selective media and identified by PCR and sequencing. Antimicrobial resistance phenotype was elucidated by the disc diffusion method, and MIC was determined by broth microdilution method according to CLSI guidelines. Detection of antimicrobial resistance and virulence genes was done by PCR. E. faecalis were isolated from 11.25% (9/80) of the clinical mastitis and 4% (1/25) of the apparently healthy cattle milk samples. The disc diffusion test revealed 40% isolates as resistant to tetracycline and azithromycin, respectively. Among them, 20% (2/10) of isolates showed resistance to both tetracycline and azithromycin. Tetracycline-resistant isolates showed MIC ranging from ≥64 to >128 μg/ml and carried tetracycline-resistant genes tetK, tetL, and tetM in 25%, 25%, and 50% of the resistant isolates, respectively. On the other hand, all the isolates were sensitive to amoxicillin, ampicillin, bacitracin, chloramphenicol, gentamicin, penicillin, and vancomycin. In addition, the isolates carried at least one of the nine virulence genes screened with pil having the highest frequency, followed by fsrB, fsrC, ace, sprE, gelE, and agg genes. Positive correlations were evident between ace, fsrC, gelE, and sprE genes that are associated with the attachment and biofilm formation in E. faecalis. E. faecalis isolated in this study carried antibiotic resistance and virulence determinants which explain their competence to be potential human pathogens.

In the past decade, the withdrawal of antibiotics used as growth promoters (AGP) has increased some poultry industry challenges, such as the rise of intestinal diseases. Experts advocate that AGPs improve performance due to the modulation of the intestinal microbiota, with resulting anti-inflammatory effects. However, the impact and interactions of AGPs with the host intestinal immune system are still unknown, which represents issues in developing effective alternatives for AGPs. Therefore, this study was aimed at better understanding the potential mechanism of action of bacitracin used as AGP and its impacts on the intestinal immune system. Ninety day-of-hatch chickens were randomly assigned to two treatments with three repetitions of fifteen birds, a control (CNT) group with a corn/soybean meal standard diet, and a control diet supplemented with 50 g/ton of feed of bacitracin (BMD). The cytokines’ and chemokines’ production (IFN-α, IFN-γ, IL-16, IL-10, IL-21, IL-6, M-CSF, MIP-3α, MIP-1β, VEGF and CCL-5) were assessed in the jejunum and ileum at 14, 21, 28 and 36 days of age by using a chicken-specific cytokine/chemokine peptide ELISA array. Broilers with BMD supplementation were found to have a lower production of IL-16, IFN-γ, M-CSF, IL-21, MIP-1β and VEGF in the jejunum at 14 d. However, from 21 through 36 days, the effect of BMD on cytokine production in the jejunum was negligible except for CCL-5, which was reduced at D36. In the ileum, BMD effects on the cytokine profile started at 28 d, when BMD-supplemented broilers showed a reduced IL-6 production level. At day 36, BMD reduced IL-16 and MIP-3α production but increased VEGF concentration in the ileum tissue. The present study demonstrated that the use of bacitracin as an AGP modulates the small intestine immune system, especially in the first phase of the broiler’s life (up to 14 days). Moreover, BMD anti-inflammatory effects include not only innate immunity but also seemed to influence the development of the adaptive immune response as seen by the decreased production of IL-21 and IL-16. These results demonstrate that a commonly used AGP in broiler feed had a local anti-inflammatory effect.

Microorganisms are important sources of various natural products that have been commercialized for human medicine and animal healthcare. Bacitracin is an important antibacterial natural product predominantly produced by Bacillus licheniformis and Bacillus subtilis, and it is characterized by a broad antimicrobial spectrum, strong activity and low resistance, thus bacitracin is extensively applied in animal feed and veterinary medicine industries. In recent years, various strategies have been proposed to improve bacitracin production. Herein, we systematically describe the regulation of bacitracin biosynthesis in genus Bacillus and its associated mechanism, to provide a theoretical basis for bacitracin overproduction. The metabolic engineering strategies applied for bacitracin production are explored, including improving substrate utilization, using an enlarged precursor amino acid pool, increasing ATP supply and NADPH generation, and engineering transcription regulators. We also present several approaches of fermentation process optimization to facilitate the industrial large-scale production of bacitracin. Finally, the challenges and prospects associated with microbial bacitracin synthesis are discussed to facilitate the establishment of high-yield and low-cost biological factories.

ABSTRACT Neisseria gonorrhoeae is a multidrug-resistant bacterial pathogen for which ceftriaxone mono-antimicrobial therapy and ceftriaxone plus azithromycin dual-antimicrobial therapy are the only remaining effective therapies. However, ceftriaxone efficacy is threatened by the global dissemination of the high-level ceftriaxone-resistant FC428 clone, while azithromycin has in recent years been removed from the recommended dual therapy in some countries as a result of increasing (high-level) azithromycin resistance. Inclusion of an alternative second antimicrobial could be an effective strategy to protect ceftriaxone from (further) resistance development. In this study, we investigated gonococcal susceptibility to bacitracin and determined its synergistic anti-gonococcal activity with ceftriaxone. Gonococcal susceptibility to bacitracin was investigated for 449 contemporary clinical isolates using the agar dilution method. Bacitracin displayed consistent activity against the N. gonorrhoeae strain collection, with a minimum inhibitory concentration (MIC) range of 2–32 mg/L and a MIC90 of 32 mg/L. Furthermore, bacitracin was bactericidal in time-kill assays, particularly against the tested FC428-associated isolate, which showed 105-fold inactivation after 8 hours of exposure to a 4× MIC dose. Importantly, bacitracin and ceftriaxone displayed synergistic activity, with a fractional inhibitory concentration index ≤0.5 for the majority of tested strains. Finally, spot assays showed strong synergistic activity against the FC428-associated isolates, with up to 200-fold reduced plating efficacy for bacitracin combined with ceftriaxone compared with ceftriaxone only. In conclusion, bacitracin shows synergistic anti-gonococcal activity with ceftriaxone and might therefore be an interesting candidate for inclusion in a dual-antimicrobial therapy with ceftriaxone. IMPORTANCE Ceftriaxone-based antimicrobial therapies for gonorrhea are threatened by waning ceftriaxone susceptibility levels and the global dissemination of the high-level ceftriaxone-resistant gonococcal FC428 clone. Combination therapy can be an effective strategy to restrain the development of ceftriaxone resistance, and for that purpose, it is important to find an alternative antimicrobial to replace azithromycin, which has recently been removed in some countries from the recommended ceftriaxone plus azithromycin dual-antimicrobial therapy. Ideally, the second antimicrobial should display synergistic activity with ceftriaxone. We hypothesized that bacitracin might display synergistic activity with ceftriaxone because of their distinct mechanisms targeting bacterial cell wall synthesis. In this study, we showed that bacitracin indeed displays synergistic activity with ceftriaxone against Neisseria gonorrhoeae. Importantly, strains associated with the FC428 clone appeared to be particularly susceptible to the bacitracin plus ceftriaxone combination, which might therefore be an interesting dual therapy for further in vivo testing.

In the past decade, the withdrawal of antibiotics used as growth promoters (AGP) has increased some poultry industry challenges, such as the rise of intestinal diseases. Experts advocate that AGPs improve performance due to the modulation of the intestinal microbiota, with resulting anti-inflammatory effects. However, the impact and interactions of AGPs with the host intestinal immune system are still unknown, which represents issues in developing effective alternatives for AGPs. Therefore, this study was aimed at better understanding the potential mechanism of action of bacitracin used as AGP and its impacts on the intestinal immune system. Ninety day-of-hatch chickens were randomly assigned to two treatments with three repetitions of fifteen birds, a control (CNT) group with a corn/soybean meal standard diet, and a control diet supplemented with 50 g/ton of feed of bacitracin (BMD). The cytokines' and chemokines' production (IFN-α, IFN-γ, IL-16, IL-10, IL-21, IL-6, M-CSF, MIP-3α, MIP-1β, VEGF and CCL-5) were assessed in the jejunum and ileum at 14, 21, 28 and 36 days of age by using a chicken-specific cytokine/chemokine peptide ELISA array. Broilers with BMD supplementation were found to have a lower production of IL-16, IFN-γ, M-CSF, IL-21, MIP-1β and VEGF in the jejunum at 14 d. However, from 21 through 36 days, the effect of BMD on cytokine production in the jejunum was negligible except for CCL-5, which was reduced at D36. In the ileum, BMD effects on the cytokine profile started at 28 d, when BMD-supplemented broilers showed a reduced IL-6 production level. At day 36, BMD reduced IL-16 and MIP-3α production but increased VEGF concentration in the ileum tissue. The present study demonstrated that the use of bacitracin as an AGP modulates the small intestine immune system, especially in the first phase of the broiler's life (up to 14 days). Moreover, BMD anti-inflammatory effects include not only innate immunity but also seemed to influence the development of the adaptive immune response as seen by the decreased production of IL-21 and IL-16. These results demonstrate that a commonly used AGP in broiler feed had a local anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

Locus SMU.243 in Streptococcus mutans was annotated as a member of the DUF2207 family proteins highly conserved in all bacteria but with unknown function. To investigate its role in S. mutans physiology, a SMU.243-deficient mutant was constructed using allelic exchange mutagenesis, and the impacts of SMU.243 deletion on bacterial growth, stress tolerance response, and biofilm formation were analyzed. Compared to the wild-type UA159, S. mutans lacking SMU.243 displayed a reduced growth rate and a reduced overnight culture density (p < 0.01) when grown at low pH and in the presence of methyl viologen. Relative to the parent strain, the deficient mutant also had a reduced survival rate following incubation in a buffer of pH 2.8 (p < 0.01) and in a buffer containing hydrogen peroxide at 58 mM after 60 min (p < 0.001) and had a reduced capacity in biofilm formation especially in the presence of sucrose (p < 0.01). To study any ensuing functional/phenotypical links between SMU.243 and uppP, which is located immediately downstream of SMU.243 and encodes an undecaprenyl pyrophosphate phosphatase involved in recycling of carrier lipid undecaprenyl phosphate, a uppP deficient mutant was generated using allelic exchange mutagenesis. Unlike the SMU.243 mutant, deletion of uppP affected cell envelope biogenesis and caused major increases in susceptibility to bacitracin. In addition, two variant morphological mutants, one forming rough colonies and the other forming mucoid, smooth colonies, also emerged following the deletion of uppP. The results suggest that the SMU.243-encoded protein of the DUF2207 family in S. mutans plays an important role in stress tolerance response and biofilm formation, but unlike the downstream uppP, does not seem to be involved in cell envelope biogenesis, although the exact roles in S. mutans' physiology awaits further investigation. [ABSTRACT FROM AUTHOR]

The food enzyme subtilisin (serine endopeptidase, EC 3.4.21.62) is produced with the non‐genetically modified microorganism Bacillus paralicheniformis strain LMG S‐30155 by ENMEX SA de CV, now part of Kerry Food Ingredients (Cork) Ltd. The food enzyme is intended to be used in oil production, hydrolysis of vegetable/microbial/animal proteins, yeast processing and production of flavouring preparations. The production strain of the food enzyme contains known antimicrobial resistance genes and genes involved in bacitracin biosynthesis. Consequently, it does not fulfil the requirements for the QPS approach to safety assessment. Bacitracin was detected in the food enzyme and the ■■■■■ The presence of bacitracin, a medically important antimicrobial, in the food enzyme represents a risk for the development of resistance in bacteria. Due to the presence of bacitracin, the Panel concluded that the food enzyme subtilisin produced with the non‐genetically modified Bacillus paralicheniformis strain LMG S‐30155 cannot be considered safe. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Comparative investigations on environmentally triggered drug delivery and wound healing characteristics of flexible hydrogel composites, Chitosan-Gelatin (C/G) and 2-Hydroxyethyl Methacrylate-Gelatin (H/G); are presented here. These composites, prepared through facile synthesis and curing methods, indicate the potential to smartly respond to the pH changes in wounds by releasing drug simultaneously and aiding in faster healing. An in-vitro investigation of the composite characteristics were included testing for Equilibrium Water Capacity Studies, Fourier Transform Infrared Spectroscopy (FTIR) investigations as well as UV based drug release and gravimetric hydrogel degradation profiles. This was followed by cutaneous application testing of the hydrogel systems in balb-c mice. Observations and testing results indicated the potential applicability of the hydrogel systems as dressings for topical/transdermal applications, provided that further detailed in-vivo characteristics are accounted for. Graphical Abstract [ABSTRACT FROM AUTHOR]

Simple Summary: Over the years, the poultry industry has relied on the use of in-feed antibiotics as a growth-promoting agent and for the prevention of diseases. However, antibiotic use has brought about pathogens that are resistant to antimicrobials. To this end, spray-dried plasma (SDP), an animal blood by-product that is rich in protein-containing lipids, peptides, immunoglobulins, transferrin, and fibrinogen, is being explored as a replacement for in-feed antibiotics in poultry. We evaluated the immunological and biochemical profile of SDP in order to understand how it enhanced performance values when supplemented to a broiler diet. At the end of the four-week study, our findings demonstrated a decrease in the number of heterophils and an increase in immunoglobulin in circulation, with oxidative stress falling in the normal range. Bifidobacteria counts also increased in the SDP-supplemented treatment. This demonstrated that SDP supplementation prevented infection and caused an increase in immunoglobulin concentration required to support intestinal development and gut microbiota modulation. Spray-dried plasma (SDP) contain a variety of functional proteins that play an immunomodulatory role. To evaluate the potential of SDP to stimulate the immune system, day-old Ross 708 male broiler chicks (200) were allocated randomly to five dietary treatments. Treatment 1 (CX) comprised chicks fed basal unmedicated corn–soybean meal (SBM) without the addition of SDP. Treatment 2 (MX) includes chicks fed unmedicated corn–SBM basal containing Bacitracin methylene disalicylate (BMD) at 0.055 g/kg diet. Treatments 3 (SDP1), 4 (SDP2), and 5 (SDP3) contained chicks given unmedicated corn–SBM basal, into which SDP was included at 10, 20, and 30 g/kg diet, respectively. On d 7, 14, and 21, chicks' body weight and FCR were calculated. Additionally, leucocyte counts, oxidative status, and IgY concentrations were determined in blood. On d 23, fecal populations of selected indicator bacteria species were determined. Results showed that FCR for SP3 was superior (p < 0.05) to other treatments. Likewise, heterophil numbers decreased in MX and SDP treatments compared to CX. Circulating IgY concentration was higher for SDP dietary treatments (p < 0.05) compared to MX. In conclusion, dietary SDP at 30 g/kg enhanced immune surveillance by increasing circulating IgY levels, maintaining a normal oxidative state, and increasing gut Bifidobacteria, thereby improving chick growth performance. [ABSTRACT FROM AUTHOR]

This study investigated intestinal oxidative damage caused by F18+ Escherichia coli and its amelioration with antibacterial bacitracin fed to nursery pigs. Thirty-six weaned pigs (6.31 ± 0.08 kg BW) were allotted in a randomized complete block design. Treatments were: NC, not challenged/not treated; PC, challenged (F18+ E. coli at 5.2 × 109 CFU)/not treated; AGP challenged (F18+ E. coli at 5.2 × 109 CFU)/treated with bacitracin (30 g/t). Overall, PC reduced (p < 0.05) average daily gain (ADG), gain to feed ratio (G:F), villus height, and villus height to crypt depth ratio (VH:CD), whereas AGP increased (p < 0.05) ADG, and G:F. PC increased (p < 0.05) fecal score, F18+ E. coli in feces, and protein carbonyl in jejunal mucosa. AGP reduced (p < 0.05) fecal score and F18+ E. coli in jejunal mucosa. PC reduced (p < 0.05) Prevotella stercorea populations in jejunal mucosa, whereas AGP increased (p < 0.05) Phascolarctobacterium succinatutens and reduced (p < 0.05) Mitsuokella jalaludinii populations in feces. Collectively, F18+ E. coli challenge increased fecal score and disrupted the microbiota composition, harming intestinal health by increasing oxidative stress, and damaging the intestinal epithelium, ultimately impairing growth performance. Dietary bacitracin reduced reduced F18+ E. coli populations and the oxidative damages they cause, thereby improving intestinal health and the growth performance of nursery pigs. [ABSTRACT FROM AUTHOR]

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In this study, bacterial isolates form Bat guano of a lime stone cave capable of producing antibiotics are reported. Screening of bacterial strains was carried out from top, middle, and bottom layer of the guano sample. Out of 20 isolated strains, three showed antimicrobial activity against all tested ATTC strain of common bacterial (both gram positive and gram negative) and fungal species. 16s RNA gene sequencing of the strain showing maximum activity revealed the isolated strain as Bacillus subtilis. Optimum production of antimicrobial compounds took place in TSB medium after 72 h of incubation at 30 °C. FTIR of crude extract showed chemical similarity with bacitracin. GCMS analysis of the crude extract revealed a range of antimicrobial and anticancer compounds. It is concluded that Bacillus subtilis strain isolated from Bat Guano is a potential source of novel antimicrobial compounds of broad-spectrum nature and have inhibitory effects against potential pathogens. [ABSTRACT FROM AUTHOR]

Deoxyribonucleic acid (DNA) can be found in saliva and various other sources. Saliva contains epithelial cells and leukocytes that are released into the oral cavity. Cells in saliva are potential sources of DNA for diagnostic purposes. DNA in saliva can be degraded due to the activity of deoxyribonuclease (DNase), an enzyme that catalyzes the hydrolysis of DNA. DNase I is expressed in exocrine cells while DNase II is expressed in macrophages. Inhibition of DNase activity will preserve DNA. Besides being able to kill bacteria, aminoglycosides (i.e. gentamicin and neomycin) can inhibit DNase. Methods: Saliva was collected from 8 subjects. Furthermore, saliva samples from each subject were divided into 4 groups, namely negative control (K1), positive control (K2), gentamicin (K3), and neomycin + bacitracin (K4). DNA was extracted from saliva using the spin column method. DNA from groups K3 and K4 were added to 1 mg/mL gentamicin and 20 mM neomycin + bacitracin, respectively, before adding 2.5 g/mL DNase I (DNA degradation assay). The quality of human genomic DNA from saliva was determined by the presence of the NOTCH2 gene amplicons (~704 bp). DNA was separated by 1% agarose gel electrophoresis and recorded using the gel documentation system. Results: The DNA extracted from saliva using the spin column method had an average concentration of 26.49 + 30.70 ng/mL and an average purity of 1.819 + 0.122. The administration of distilled water as a negative control in the DNA degradation assay showed that no DNA was digested. Gentamicin inhibited the activity of 2.5 mg/mL of DNase I at a concentration of 35 g/mL while neomycin + bacitracin inhibited it at a concentration of 0.8 mM. Conclusion: Certain levels of gentamicin and neomycin+ bacitracin inhibited the activity of 2.5 mg/mL DNase I and maintained the quality of human genomic DNA from saliva. [ABSTRACT FROM AUTHOR]