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Poultry Science Oct 2022Necrotic enteritis causes economic losses estimated to be up to 6 billion US dollars per year. Clinical and subclinical infections in poultry are also both correlated...
Necrotic enteritis causes economic losses estimated to be up to 6 billion US dollars per year. Clinical and subclinical infections in poultry are also both correlated with decreased growth and feed efficiency. Moreover, in a context of increased antibiotic resistance, feed additives with enhanced antimicrobial properties are a useful and increasingly needed strategy. In this study, the protective effects of a blend of thymol and organic acids against the effects of Clostridium perfringens type A (CP) on chicken intestinal epithelial cells were investigated and compared to bacitracin, a widely used antibiotic in poultry production. Primary chicken intestinal epithelial cells were challenged with CP for a total time of 3 h to assess the beneficial effect of 2 doses of citric acid, dodecanoic acid, and thymol-containing blend, and compare them with bacitracin. During the challenge, different parameters were recorded, such as transepithelial electrical resistance, cell viability, mRNA expression, and reactive oxygen species production. CP induced inflammation with cytokine production and loss of epithelial barrier integrity. It was also able to induce reactive oxygen species production and increase the caspase expression leading to cellular death. The high dose of the blend acted similarly to bacitracin, preventing the disruptive effects of CP and inducing also an increase in zonula occludens-1 mRNA expression. The low dose only partially prevented the disruptive effects of CP but successfully reduced the associated inflammation. This study shows that the usage of thymol combined with 2 organic acids can protect primary chicken intestinal epithelial cells from CP-induced damages creating a valid candidate to substitute or adjuvate the antibiotic treatment against necrotic enteritis.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacitracin; Caspases; Chickens; Citric Acid; Clostridium Infections; Clostridium perfringens; Cytokines; Enteritis; Epithelial Cells; Inflammation; Lauric Acids; Poultry; Poultry Diseases; RNA, Messenger; Reactive Oxygen Species; Thymol
PubMed: 36088896
DOI: 10.1016/j.psj.2022.102101 -
[Enhanced production of bacitracin via energy metabolism engineering in Bacillus licheniformis DW2].Sheng Wu Gong Cheng Xue Bao = Chinese... Jun 2020Bacitracin is a broad-spectrum cyclic peptide antibiotic, and mainly produced by Bacillus. Energy metabolism plays as a critical role in high-level production of target...
Bacitracin is a broad-spectrum cyclic peptide antibiotic, and mainly produced by Bacillus. Energy metabolism plays as a critical role in high-level production of target metabolites. In this study, Bacillus licheniformis DW2, an industrial strain for bacitracin production, was served as the original strain. First, our results confirmed that elimination of cytochrome bd oxidase branch via deleting gene cydB benefited bacitracin synthesis. Bacitracin titer and ATP content were increased by 10.97% and 22.96%, compared with those of original strain, respectively. Then, strengthening cytochrome aa3 oxidase branch via overexpressing gene qoxA was conducive to bacitracin production. Bacitracin titer and ATP content were increased by 18.97% and 34.00%, respectively. In addition, strengthening ADP synthesis supply is also proven as an effective strategy to promote intracellular ATP accumulation, overexpression of adenosine kinase DcK and adenylate kinase AdK could all improve bacitracin titers, among which, dck overexpression strain showed the better performance, and bacitracin titer was increased by 16.78%. Based on the above individual methods, a method of combining the deletion of gene cydB and overexpression of genes qoxA, dck were used to enhance ATP content of cells to 39.54 nmol/L, increased by 49.32% compared to original strain, and bacitracin titer produced by the final strain DW2-CQD (DW2ΔcydB::qoxA::dck) was 954.25 U/mL, increased by 21.66%. The bacitracin titer produced per cell was 2.11 U/CFU, increased by 11.05%. Collectively, this study demonstrates that improving ATP content was an efficient strategy to improve bacitracin production, and a promising strain B. licheniformis DW2-CQD was attained for industrial production of bacitracin.
Topics: Bacillus licheniformis; Bacitracin; Energy Metabolism; Industrial Microbiology
PubMed: 32597062
DOI: 10.13345/j.cjb.190464 -
International Journal of Molecular... Apr 2022The β1-integrin receptor is broadly expressed on tumor and other cells in the tumor microenvironment (TME), and is an unfavorable prognostic factor for cancers....
The β1-integrin receptor is broadly expressed on tumor and other cells in the tumor microenvironment (TME), and is an unfavorable prognostic factor for cancers. Nature-derived resveratrol has preventive and apoptotic effects on tumors, but whether resveratrol can exert its suppressive actions on TME-induced tumorigenesis through β1-integrin on the surface of CRC cells is still unknown. HCT116 or SW480 cells were exposed to inhibitory antibodies against β1-integrin, bacitracin (selective β1-integrin inhibitor), integrin-binding RGD (Arg-Gly-Asp) peptide, and/or resveratrol. We evaluated the anti-tumor actions and signaling impacts of resveratrol in colorectal cancer (CRC)-TME. We found that resveratrol completely altered the β1-integrin distribution pattern and expression on the surface of CRC cells in TME. Moreover, resveratrol down-regulated CRC cell proliferation, colony formation, viability, and up-regulated apoptosis in a concentration-dependent way. These actions of resveratrol were antagonized mainly by inhibitory antibodies against β1-integrin but not β5-integrin, and by an integrin-binding RGD peptide but not by RGE peptide, and by bacitracin in TME. Similarly, resveratrol-blocked TME-induced p65-NF-kB and its promoted gene markers linked to proliferation (cyclin D1), invasion (focal adhesion kinase, FAK), or apoptosis (caspase-3), were largely abrogated by anti-β1-integrin or RGD peptide, suggesting that β1-integrin is a potential transmission pathway for resveratrol/integrin down-stream signaling in CRC cells. The current results highlight, for the first time, the important gateway role of β1-integrins as signal carriers for resveratrol on the surfaces of HCT116 and SW480 cells, and their functional cooperation for the modulatory effects of resveratrol on TME-promoted tumorigenesis.
Topics: Bacitracin; Carcinogenesis; Humans; Integrin beta1; Resveratrol; Signal Transduction; Tumor Microenvironment
PubMed: 35563105
DOI: 10.3390/ijms23094714 -
Applied and Environmental Microbiology Nov 2012Bacillus spp. are widely used as feed additives and probiotics. However, there is limited information on their resistance to various antibiotics, and there is a growing...
Antimicrobial susceptibility of Bacillus strains isolated from primary starters for African traditional bread production and characterization of the bacitracin operon and bacitracin biosynthesis.
Bacillus spp. are widely used as feed additives and probiotics. However, there is limited information on their resistance to various antibiotics, and there is a growing concern over the transfer of antibiotic resistance genes. The MIC for 8 antibiotics was determined for 85 Bacillus species strains, Bacillus subtilis subsp. subtilis (n = 29), Bacillus licheniformis (n = 38), and Bacillus sonorensis (n = 18), all of which were isolated from starters for Sudanese bread production. All the strains were sensitive to tetracycline (8.0 mg/liter), vancomycin (4.0 mg/liter), and gentamicin (4.0 mg/liter) but resistant to streptomycin. Sensitivity to clindamycin, chloramphenicol, and kanamycin was species specific. The erythromycin resistance genes ermD and ermK were detected by PCR in all of the erythromycin-resistant (MIC, ≥16.0 mg/liter) B. licheniformis strains and one erythromycin-sensitive (MIC, 4.0 mg/liter) B. licheniformis strain. Several amino acid changes were present in the translated ermD and ermK nucleotide sequences of the erythromycin-sensitive strain, which could indicate ErmD and ErmK protein functionalities different from those of the resistance strains. The ermD and ermK genes were localized on an 11.4-kbp plasmid. All of the B. sonorensis strains harbored the bacitracin synthetase gene, bacA, and the transporter gene bcrA, which correlated with their observed resistance to bacitracin. Bacitracin was produced by all the investigated species strains (28%), as determined by ultra-high-definition quadrupole time-of-flight liquid chromatography-mass spectrometry (UHD-QTOF LC/MS). The present study has revealed species-specific variations in the antimicrobial susceptibilities of Bacillus spp. and provides new information on MIC values, as well as the occurrence of resistance genes in Bacillus spp., including the newly described species B. sonorensis.
Topics: Anti-Bacterial Agents; Bacillus; Bacitracin; Bread; Chromatography, Liquid; Mass Spectrometry; Metabolic Networks and Pathways; Microbial Sensitivity Tests; Molecular Sequence Data; Operon; Sequence Analysis, DNA
PubMed: 22941078
DOI: 10.1128/AEM.00730-12 -
Microbiology Spectrum Feb 2023Breast implant-associated infections (BIAIs) are the primary complication following placement of breast prostheses in breast cancer reconstruction. Given the prevalence...
Breast implant-associated infections (BIAIs) are the primary complication following placement of breast prostheses in breast cancer reconstruction. Given the prevalence of breast cancer, reconstructive failure due to infection results in significant patient distress and health care expenditures. Thus, effective BIAI prevention strategies are urgently needed. This study tests the efficacy of one infection prevention strategy: the use of a triple antibiotic pocket irrigant (TAPI) against Staphylococcus aureus, the most common cause of BIAIs. TAPI, which consists of 50,000 U bacitracin, 1 g cefazolin, and 80 mg gentamicin diluted in 500 mL of saline, is used to irrigate the breast implant pocket during surgery. We used and assays to test the efficacy of each antibiotic in TAPI, as well as TAPI at the concentration used during surgery. We found that planktonically grown S. aureus BIAI isolates displayed susceptibility to gentamicin, cefazolin, and TAPI. However, TAPI treatment enhanced biofilm formation of BIAI strains. Furthermore, we compared TAPI treatment of a S. aureus reference strain (JE2) to a BIAI isolate (117) in a mouse BIAI model. TAPI significantly reduced infection of JE2 at 1 and 7 days postinfection (dpi). In contrast, BIAI strain 117 displayed high bacterial burdens in tissues and implants, which persisted to 14 dpi despite TAPI treatment. Lastly, we demonstrated that TAPI was effective against Pseudomonas aeruginosa reference (PAO1) and BIAI strains and Together, these data suggest that S. aureus BIAI strains employ unique mechanisms to resist antibiotic prophylaxis treatment and promote chronic infection. The incidence of breast implant associated infections (BIAIs) following reconstructive surgery postmastectomy remains high, despite the use of prophylactic antibiotic strategies. Thus, surgeons have begun using additional antibiotic-based prevention strategies, including triple antibiotic pocket irrigants (TAPIs). However, these strategies fail to reduce BIAI rates for these patients. To understand why these therapies fail, we assessed the antimicrobial resistance patterns of Staphylococcus aureus strains, the most common cause of BIAI, to the antibiotics in TAPI (bacitracin, cefazolin, and gentamicin). We found that while clinically relevant BIAI isolates were more susceptible to the individual antibiotics compared to a reference strain, TAPI was effective at killing all the strains . However, in a mouse model, the BIAI isolates displayed recalcitrance to TAPI, which contrasted with the reference strain, which was susceptible. These data suggest that strains causing BIAI may encode specific recalcitrance mechanisms not present within reference strains.
Topics: Animals; Mice; Anti-Bacterial Agents; Staphylococcus aureus; Cefazolin; Breast Implants; Bacitracin; Mastectomy; Staphylococcal Infections; Polymyxin B; Gentamicins; Microbial Sensitivity Tests
PubMed: 36507629
DOI: 10.1128/spectrum.02884-22 -
Current Alzheimer Research Jan 2012In Alzheimer's disease, histochemically visualized cholinesterases with altered pH optimum for activity and inhibitable by indoleamines and the protease inhibitor...
In Alzheimer's disease, histochemically visualized cholinesterases with altered pH optimum for activity and inhibitable by indoleamines and the protease inhibitor bacitracin emerge in association with plaques and tangles. It has been suggested that these cholinesterases may participate in the pathologic process. However, it is not known whether the properties of cholinesterases observed in Alzheimer's disease are due to requirements of histochemical procedures or actual biochemical properties of these enzymes. Using biochemical assays of acetylcholinesterase and butyrylcholinesterase activities, we demonstrate here that serotonin and bacitracin result in a significantly greater and dose-dependent inhibition of cholinesterases in Alzheimer's disease cortex when compared with age-matched controls. In contrast, variations in pH did not distinguish cholinesterases in Alzheimer's disease and control cortex. We also confirmed significant reduction of acetylcholinesterase activity in Alzheimer's disease cortex and increased butyrylcholinesterase activity that only approached significance. We conclude that inhibition by indoleamines and bacitracin is a biochemical characteristic of a proportion of cholinesterases in Alzheimer's disease that most likely represents the pool associated with plaques and tangles. Most of the available cholinesterase inhibitors are relatively incapable of inhibiting cholinesterases associated with plaques and tangles. The findings of the present investigation open the way for attempts to isolate cholinesterases associated with plaques and tangles and design or discovery of inhibitors specifically targeted to cholinesterases in these lesions.
Topics: Acetylcholinesterase; Aged; Aged, 80 and over; Alzheimer Disease; Autopsy; Bacitracin; Butyrylcholinesterase; Case-Control Studies; Cerebral Cortex; Detergents; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Humans; Hydrogen-Ion Concentration; Male; Octoxynol; Polysorbates; Serotonin
PubMed: 21244353
DOI: 10.2174/156720512799015127 -
Scientific Reports Jul 2020With the ever-increasing availability of whole-genome sequences, machine-learning approaches can be used as an alternative to traditional alignment-based methods for...
With the ever-increasing availability of whole-genome sequences, machine-learning approaches can be used as an alternative to traditional alignment-based methods for identifying new antimicrobial-resistance genes. Such approaches are especially helpful when pathogens cannot be cultured in the lab. In previous work, we proposed a game-theory-based feature evaluation algorithm. When using the protein characteristics identified by this algorithm, called 'features' in machine learning, our model accurately identified antimicrobial resistance (AMR) genes in Gram-negative bacteria. Here we extend our study to Gram-positive bacteria showing that coupling game-theory-identified features with machine learning achieved classification accuracies between 87% and 90% for genes encoding resistance to the antibiotics bacitracin and vancomycin. Importantly, we present a standalone software tool that implements the game-theory algorithm and machine-learning model used in these studies.
Topics: Anti-Bacterial Agents; Bacitracin; Bacteria; Computational Biology; Drug Resistance, Bacterial; Game Theory; Machine Learning; Microbial Sensitivity Tests; Software; Vancomycin; Whole Genome Sequencing
PubMed: 32620856
DOI: 10.1038/s41598-020-67949-9 -
Diabetes, Obesity & Metabolism Aug 2020Haemolysis of serially collected insulin serum samples frequently causes falsely-low measured concentrations because of the release of intracellular insulin degrading...
Haemolysis of serially collected insulin serum samples frequently causes falsely-low measured concentrations because of the release of intracellular insulin degrading enzyme (IDE). We investigated if bacitracin, an in vitro IDE inhibitor, could prevent haemolysis-induced insulin degradation during insulin sensitivity testing. Blood samples were collected from adults undergoing serial sampling for insulin sensitivity. A dose-finding study measured insulin from experimentally haemolysed samples containing five bacitracin concentrations (0-2.5 g/L) and from non-experimentally haemolysed samples. To confirm the utility of bacitracin in the clinical setting, we compared insulin in samples collected with and without 1 g/L bacitracin from a frequently sampled intravenous glucose tolerance test (FSIVGTT), where haemolysis often occurs accidentally. In the dose-finding study, bacitracin 0.25, 1 and 2.5 g/L all maximally prevented insulin degradation in experimentally haemolysed samples. Among FSIVGTT unintentionally haemolysed samples, insulin concentrations from bacitracin-containing samples were significantly higher than from those without bacitracin (P < .01), and not different from non-haemolysed samples obtained simultaneously from a second intravenous catheter (P = .07). Bacitracin did not significantly alter insulin concentrations in non-haemolysed samples. Bacitracin attenuates haemolysis-associated insulin degradation in clinical samples, enabling a more accurate assessment of insulin sensitivity and glucose homeostasis.
Topics: Adult; Bacitracin; Drug Repositioning; Hemolysis; Humans; Insulin; Insulin Resistance; Pharmaceutical Preparations
PubMed: 32227616
DOI: 10.1111/dom.14038 -
Journal of Bacteriology May 1964Hancock, R. (Harvard Medical School, Boston, Mass.), and P. C. Fitz-James. Some differences in the action of penicillin, bacitracin, and vancomycin on Bacillus...
Hancock, R. (Harvard Medical School, Boston, Mass.), and P. C. Fitz-James. Some differences in the action of penicillin, bacitracin, and vancomycin on Bacillus megaterium. J. Bacteriol. 87:1044-1050. 1964.-Penicillin and cycloserine do not inhibit the growth of protoplasts of Bacillus megaterium, indicating that inhibition of cell-wall synthesis is the only significant process by which they inhibit growth of bacteria. In contrast, bacitracin and vancomycin inhibit growth of protoplasts and bacteria at similar concentrations, indicating that they have important sites of action other than their known inhibition of cell-wall synthesis. At concentrations which inhibit mucopeptide synthesis, penicillin, bacitracin, and vancomycin each cause an increased rate of efflux of K ions from growing bacteria. This effect of penicillin is prevented by chloramphenicol or hypertonic sucrose, whereas the effects of bacitracin and vancomycin are unchanged under these conditions. It is concluded that bacitracin and vancomycin have direct effects on the cytoplasmic membrane, and it is proposed that their inhibition of cell-wall synthesis could be a consequence of these effects. Bacitracin and vancomycin do not compete with penicillin for binding to cells of B. megaterium, a further indication that they have a different primary site of action.
Topics: Bacillus megaterium; Bacitracin; Cell Membrane Permeability; Cell Wall; Cycloserine; Mucoproteins; Novobiocin; Penicillin G; Potassium; Potassium Isotopes; Protoplasts; Vancomycin
PubMed: 4959792
DOI: 10.1128/jb.87.5.1044-1050.1964 -
Clinical Breast Cancer Apr 2023The current standard of practice in implant-based breast reconstruction is irrigation of the mastectomy pocket with antimicrobial solution before implant placement....
INTRODUCTION
The current standard of practice in implant-based breast reconstruction is irrigation of the mastectomy pocket with antimicrobial solution before implant placement. Prior to being banned and formally recalled in January 2020, bacitracin was a very commonly utilized antibiotic. This study characterizes the effects of the national bacitracin ban on implant-based breast reconstruction infection rates by using a nationwide database to compare complication rates before and after bacitracin was banned.
MATERIALS AND METHODS
The American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) database was queried retrospectively for all patients who underwent implant-based breast reconstruction before the bacitracin ban (2012-2019) and afterwards (2020). Demographics, comorbidities, and complications were collected. Univariate analysis and multivariate analysis were conducted to determine if there were significant changes in wound complications, local wound infections, and systemic infections between the 2 case-control matched cohorts.
RESULTS
A total of 37,126 patients were in the pre-ban cohort and 6333 patients were in the post-ban cohort. Before matching, there were significant differences in race distribution, BMI, ASA class, inpatient vs. outpatient status, preoperative smoking, and preoperative diabetes mellitus (all P < .05). After case-control matching, there were 6313 patients in each cohort. Univariate analysis revealed differences in postoperative superficial and organ space surgical site infection, wound complications/infections, all cause complications, and reoperations (all P < .05). Multivariate analysis showed that patients who underwent breast reconstruction before the ban had decreased odds of having wound infections, related infections, all cause complications, and reoperations (all P < .05).
CONCLUSION
This study provides a macroscopic view into the effects of the formal injectable bacitracin ban on breast reconstruction outcomes. Patients who underwent implant-based breast reconstruction after the ban of injectable bacitracin had higher odds of developing wound infections, related infections, and reoperations. More study into suitable alternatives to injectable bacitracin for surgical site antimicrobial irrigation is warranted.
Topics: Humans; Female; Mastectomy; Bacitracin; Retrospective Studies; Breast Neoplasms; Mammaplasty; Surgical Wound Infection; Postoperative Complications; Breast Implants
PubMed: 36658063
DOI: 10.1016/j.clbc.2022.12.019