Potentiality of phytobiotics to counter prevalent bacteria vis-a-vis to replace use of antibiotics in poultry
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PROVIDER: PRJEB28289 | ENA |
REPOSITORIES: ENA
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Project description:IntroductionAntimicrobial resistance (AMR) is a global issue that needs addressing. While antibiotic stewardship has improved often by restricting antibiotic use, some antibiotics that are still sold legally over the counter (OTC), notably in sore throat medications. Recent findings suggest OTC antibiotics could trigger cross-resistance to antibiotics used in clinical treatments, whether systemic or topical. Here we investigated the impact of three antibiotics contained in OTC sore throat medicines on emerging AMR in vitro.MethodsBacterial pathogens were exposed to a bactericidal concentration of an aminoglycoside in the presence or absence of a during-use concentration of bacitracin, gramicidin or tyrothricin in a time-kill assay. Damage to the bacterial membrane was also investigated by measuring potassium leakage and membrane potential alteration post-OTC antibiotic exposure.ResultsGramicidin (15 µg/mL) significantly decreased the bactericidal activity of amikacin, tobramycin or gentamicin in Acinetobacter baumannii. It also decreased gentamicin bactericidal activity in Enterobacter cloacae, Escherichia coli and Klebsiella pneumoniae, while tyrothricin decreased the aminoglycoside efficacy in E. cloacae and E. coli. Gramicidin significantly decreased bacterial membrane potential and caused significant potassium leakage.ConclusionGramicidin and to some extent tyrothricin impacted aminoglycoside efficacy by affecting membrane potential, which is essential for aminoglycosides uptake. Thus, some OTC antibiotics can interfere with aminoglycoside activity, which could in turn affect treatment efficacy. Although the likelihood of OTC antibiotics and aminoglycosides being used at the same time might not be common, this research highlights one potential reason for OTC antibiotics' usage to result in treatment failure and their contribution to AMR development.
| S-EPMC11695918 | biostudies-literature
Project description:ObjectivesThis study was conducted to assess poultry farmers' knowledge and practices regarding antibiotics, antimicrobial usage (AMU), and antimicrobial resistance (AMR), and to identify the sociodemographic factors of inappropriate use of antibiotics in commercial poultry farms in Bangladesh.MethodsA qualitative survey of 140 farmers in Bangladesh was conducted from March to May 2019. A logistic regression model was used to identify factors associated with the inappropriate use of antibiotics.Results47.1% of farmers were unable to explain antibiotics, 42.9% used antibiotics for preventive purposes, 4.3% used them as growth promoters, 25.7% used them as suggested by veterinarians, 42.9% used leftover antibiotics, 50% did not maintain antibiotics residual withdrawal period, and 98.6% did not know about AMR. In bivariable regression analysis, sex and primary occupation of poultry farmers, their knowledge about withdrawal periods for antibiotics, and no contact with veterinary surgeons (VS) were found to be significantly associated with the inappropriate use of antibiotics, while only 'no contact with VS' was identified in multivariable regression analysis.ConclusionsThe findings suggest an urgent need to improve understanding of antibiotics and AMR. Adequate supervision by veterinarians would ensure adherence to appropriate AMU patterns, and would limit the misuse of antibiotics and associated AMR development in farms.
| S-EPMC10112016 | biostudies-literature
Project description:Inappropriate antibiotic use in food-producing animals is associated with the emergence and spread of antibiotic resistance. In industrial broiler poultry farms in three districts of Kathmandu valley, Nepal, we assessed antibiotic use prevalence, and their classes, types, and quantities. A cross-sectional questionnaire study involving field visits to large poultry farms (flock size ≥ 3000) of the Kathmandu, Bhaktapur, and Lalitpur districts was conducted. Of 30 farms (total flock size 104,200; range 3000-6000), prevalence of antibiotic use was 90% (95% CI: 73-98%). Six (22%) farms used antibiotics as prophylaxis, while 21 (78%) used it for therapeutics. Seven antibiotics from six classes (including quinolones, macrolides, and polymyxins) were used. The most commonly used antibiotics were tylosin (47%), colistin (47%), and dual therapies with neomycin and doxycycline (33%). A total of 50,000 grams of antibiotics (total weight including active and inactive ingredients) were used (0.5 grams/chicken/45 days of flock life) with eight (26%) farms using more than two antibiotics. No farms had records on clinical indications for prophylaxis or treatment. No post-mortem records of sick birds were available. Prevalence of antibiotic use in broiler farms of Kathmandu valley is high and includes "highest priority critically important antibiotics" for human use, with direct implications on public health.
| S-EPMC8167706 | biostudies-literature
Project description:Previously, we have shown that broad spectrum antibiotic treatment reduces reactive astrocyte phenotypes in the APPPS1-21 model of AD-related amyloidosis. We have also found that antibiotics selectively increases propionate levels and exogenous propionate treatment recapitulates phenotypes observed in antibiotic treated mice. In the current study, we wanted to assess astrocyte transcriptional state using bulk RNA sequencing. To accomplish this we used translating ribosome affinity purification (TRAP) sequencing, a ribosomal protein L10a is fused to eGFP under the control of a cell type specific promoter in a transgenic mouse model. We crossed APPPS1-21 mice to the Aldh1l1-eGFP/Rpl10a bacTRAP mouse model and progeny were treated with antibiotics, propionate, or VHL and performed bulk TRAPseq.
2025-05-01 | GSE295458 | GEO
Project description:The inappropriate use of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) infection as an example and show that imipenem increases the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrate that imipenem enhances the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promotes the phagocytosis of OMVs by macrophages that depends on the interaction between GroEL and its receptor LOX-1. OMVs cause the pyroptosis of macrophages and the release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We propose that the inappropriate use of antibiotics in the cases of infection by MDR bacteria such as K. pneumoniae might cause damaging inflammatory responses, which underlines the pernicious effects of inappropriate use of antibiotic.
2021-08-28 | GSE182766 | GEO
Project description:Combination therapy is rarely used to counter the evolution of resistance in bacterial infections. Expansion of the use of combination therapy requires knowledge of how drugs interact at inhibitory concentrations. More than 50 years ago, it was noted that, if bactericidal drugs are most potent with actively dividing cells, then the inhibition of growth induced by a bacteriostatic drug should result in an overall reduction of efficacy when the drug is used in combination with a bactericidal drug. Our goal here was to investigate this hypothesis systematically. We first constructed time-kill curves using five different antibiotics at clinically relevant concentrations, and we observed antagonism between bactericidal and bacteriostatic drugs. We extended our investigation by performing a screen of pairwise combinations of 21 different antibiotics at subinhibitory concentrations, and we found that strong antagonistic interactions were enriched significantly among combinations of bacteriostatic and bactericidal drugs. Finally, since our hypothesis relies on phenotypic effects produced by different drug classes, we recreated these experiments in a microfluidic device and performed time-lapse microscopy to directly observe and quantify the growth and division of individual cells with controlled antibiotic concentrations. While our single-cell observations supported the antagonism between bacteriostatic and bactericidal drugs, they revealed an unexpected variety of cellular responses to antagonistic drug combinations, suggesting that multiple mechanisms underlie the interactions.
| S-EPMC4135978 | biostudies-literature
Project description:The goal of this project is to develop a new class of urea-depsipeptide (UDEP) antibiotics to treat prosthetic joint infections (PJI). UDEPs kill bacteria through activation of the ClpP protease, causing cells to self-digest. This unique activating mechanism allows UDEPs to kill biofilms and non-growing persister cells, which are prevalent in PJI and explain why current antibiotics are largely ineffective. Current therapies involve weeks to months of antibiotic treatment, debridement surgeries, and medical device replacement. UDEPs have the potential to minimize surgical interventions due to PJI and improve patient care. PJI are primarily caused by the Gram-positive pathogens Staphylococcus aureus and epidermidis and the UDEPs are potently active against these pathogens, including multi-drug resistant strains. A recent advance in our UDEP medical chemistry program yielded a new compound which has improved safety, solubility, and bone penetration compared to first generation UDEPs. A preliminary study found that the compound was effective in a K-wire femur medullary canal implant model of PJI, which is known to be difficult to treat. In this project, we will evaluate if the compound is an acceptable pre-clinical candidate for PJI by testing it in a series of in vitro and in vivo studies focused on this indication. Specifically, the aims are to 1) scale up the compound; 2) determine the microbiological and biofilm killing effect against the main pathogens isolated from PJI; and 3) determine the efficacy of the compound in mouse and rabbit models of PJI.
2025-06-12 | GSE270632 | GEO
Project description:Understanding how M. tuberculosis survives during antibiotic treatment is necessary to rationally devise more effective tuberculosis chemotherapy regimens. Using genome-wide mutant fitness profiling and the mouse model of TB, we identified genes that alter antibiotic efficacy specifically in the infection environment.
2020-07-18 | GSE154627 | GEO
Project description:Widespread availability of antibiotics without prescription potentially facilitates overuse and contributes to selection pressure for antimicrobial resistant bacteria. Prior to this study, anecdotal observations in Guatemala identified corner stores as primary antibiotic dispensaries, where people purchase antibiotics without prescriptions. We carried out a cross sectional study to document the number and types of antibiotics available in corner stores, in four study areas in Guatemala. A total of 443 corner stores were surveyed, of which 295 (67%) sold antibiotics. The most commonly available antibiotics were amoxicillin, found in 246/295 (83%) stores, and tetracycline, found in 195/295 (66%) stores. Over the counter sales result from laissez-faire enforcement of antibiotic dispensing regulations in Guatemala combined with patient demand. This study serves as a baseline to document changes in the availability of antibiotics in informal establishments in light of new pharmacy regulations for antibiotic dispensing, which were adopted after this study was completed.
| S-EPMC7518585 | biostudies-literature
Project description:Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part, by inducing production of damaging reactive species. This notion has been supported by many groups, but recently challenged. Here we robustly test the hypothesis using biochemical, enzymatic and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular hydrogen peroxide (H2O2) sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species, to demonstrate that antibiotics broadly induce redox stress. Subsequent gene expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supra-physiological levels of H2O2. We next developed a method to dynamically quantify cellular respiration and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that catalase or DNA mismatch repair enzyme overexpression, as well as antioxidant pre-treatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions, but could be enhanced by exposure to molecular oxygen or addition of alternative electron acceptors, suggesting that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that bactericidal antibiotics, downstream of their target-specific interactions, induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality. Here, we used microarrays to analyze oxidative stress responses to bactericidal antibiotic treatment in wildtype and mutant E coli
2014-04-02 | GSE56133 | GEO