scholarly journals Bio-Engineered Nisin with Increased Anti-Staphylococcus and Selectively Reduced Anti-Lactococcus Activity for Treatment of Bovine Mastitis

2021 ◽  
Vol 22 (7) ◽  
pp. 3480
Author(s):  
Des Field ◽  
Kiera Considine ◽  
Paula M. O’Connor ◽  
R. Paul Ross ◽  
Colin Hill ◽  
...  

Bovine mastitis is a significant economic burden for dairy enterprises, responsible for premature culling, prophylactic and therapeutic antibiotic use, reduced milk production and the withholding (and thus wastage) of milk. There is a desire to identify novel antimicrobials that are expressly directed to veterinary applications, do not require a lengthy milk withholding period and that will not have a negative impact on the growth of lactic acid bacteria involved in downstream dairy fermentations. Nisin is the prototypical lantibiotic, a family of highly modified antimicrobial peptides that exhibit potent antimicrobial activity against many Gram-positive microbes, including human and animal pathogens including species of Staphylococcus and Streptococcus. Although not yet utilized in the area of human medicine, nisin is currently applied as the active agent in products designed to prevent bovine mastitis. Over the last decade, we have harnessed bioengineering strategies to boost the specific activity and target spectrum of nisin against several problematic microorganisms. Here, we screen a large bank of engineered nisin derivatives to identify novel derivatives that exhibit improved specific activity against a selection of staphylococci, including mastitis-associated strains, but have unchanged or reduced activity against dairy lactococci. Three such peptides were identified; nisin A M17Q, nisin A T2L and nisin A HTK.

PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0218134 ◽  
Author(s):  
Koen B. Pouwels ◽  
Berit Muller-Pebody ◽  
Timo Smieszek ◽  
Susan Hopkins ◽  
Julie V. Robotham

Author(s):  
Ana Rita Almeida ◽  
Marta Tacão ◽  
Joana Soares ◽  
Inês Domingues ◽  
Isabel Henriques

The emergence of antibiotic-resistant pathogens due to worldwide antibiotic use is raising concern in several settings, including aquaculture. In this work, the selection of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) was evaluated after exposure of zebrafish to oxytetracycline (OTC) for two months, followed by a recovery period. The selection of ARB in water and fish was determined using selective media. The abundance of tetA genes was estimated through qPCR. Higher prevalence of ARB was measured in all samples exposed to the antibiotic when compared to control samples, although statistical significance was only achieved five days after exposure. Isolates recovered from samples exposed to the antibiotic were affiliated with Pseudomonas and Stenotrophomonas. Various antibiotic susceptibility profiles were detected and 37% of the isolates displayed multidrug resistance (MDR). The selection of the tetA gene was confirmed by qPCR at the highest OTC concentration tested. Two MDR isolates, tested using zebrafish embryos, caused significant mortality, indicating a potential impact on fish health and survival. Overall, our work highlights the potential impact of antibiotic contamination in the selection of potential pathogenic ARB and ARGS.


1938 ◽  
Vol 21 (3) ◽  
pp. 335-366 ◽  
Author(s):  
John H. Northrop

1. A method for isolating a nucleoprotein from lysed staphylococci culture is described. 2. It is homogeneous in the ultracentrifuge and has a sedimentation constant of 650 x 10–13 cm. dyne–1 sec.–1, corresponding to a molecular weight of about 300,000,000. 3. The diffusion coefficient varies from about 0.001 cm.2/day in solutions containing more than 0.1 mg. protein/ml. to 0.02 in solutions containing less than 0.001 mg. protein/ml. The rate of sedimentation also decreases as the concentration decreases. It is suggested, therefore, that this protein exists in various sized molecules of from 500,000–300,000,000 molecular weight, the proportion of small molecules increasing as the concentration decreases. 4. This protein is very unstable and is denatured by acidity greater than pH 5.0, by temperature over 50°C. for 5 minutes. It is digested by chymo-trypsin but not by trypsin. 5. The loss in activity by heat, acid, and chymo-trypsin digestion is roughly proportional to the amount of denatured protein formed under these conditions. 6. The rate of diffusion of the protein is the same as that of the active agent. 7. The rate of sedimentation of the protein is the same as that of the active agent. 8. The loss in activity when susceptible living or dead bacteria are added to a solution of the protein is proportional to the loss in protein from the solution. Non-susceptible bacteria remove neither protein nor activity. 9. The relative ultraviolet light absorption, as determined directly, agrees with that calculated from Gates' inactivation experiments in the range of 2500–3000 Å. u. but is somewhat greater in the range of 2000–2500 Å. u. 10. Solubility determinations showed that most of the preparations contained at least two proteins, one being probably the denatured form of the other. Two preparations were obtained, however, which had about twice the specific activity of the earlier ones and which gave a solubility curve approximating that of a pure substance. 11. It is suggested that the formation of phage may be more simply explained by analogy with the autocatalytic formation of pepsin and trypsin than by analogy with the far more complicated system of living organisms.


Author(s):  
Oksana Yurynets ◽  

Currently, many Ukrainian enterprises are in crisis. Getting out of this situation requires the use of various types of urgent crisis management tools, among which investment instruments play an important role. The purpose of this article is to form the theoretical basis for the use of urgent investment tools of crisis management at enterprises. It was found that the urgent investment tools of crisis management in the enterprise should be understood as ways of immediate (urgent) investment actions which are aimed at eliminating or reducing the negative impact of the crisis on the economic condition of the enterprise and ensuring its further effective development. These instruments are grouped according to the following characteristics: the environment in which the relevant instruments are formed and operate, the relation to the current owners of the enterprise, the effectiveness of implementation, the duration of the effect of implementing instruments, the urgency of their implementation, the areas of investment, the objectives of application, the duration of application, the types of financial and economic crises at the enterprise, the elimination (reduction) of the negative influence of which the corresponding tools are directed at, the subject of investment. It is established that the main tasks of using investment urgent tools of anti-crisis management at the enterprises are: selection of the best types of investment urgent tools of anti-crisis management; selection of the best variant of each type of urgent investment tools of crisis management; setting deadlines for the implementation of selected types and options for urgent tools of crisis management at the enterprise; determination of the optimal amount of total investments that should be invested in the implementation of the crisis management program at the enterprise, and the corresponding to this volume of the general list of investment urgent tools of such management; identifying the best sources of investment and establishing the best structure of investment in terms of these sources.


Author(s):  
L.L. Zakharova ◽  
◽  
G.A. Zhorov ◽  
V.I. Dorozhkin ◽  
◽  
...  

Negative impact on the environment as a result of economic activity of man increasingly becomes the character of combined pollution of ecotoxicants, including xenobiotics of radiation and chemical nature. In animal husbandry in ecologically unfavorable regions, sorbtion-detoxication technologies based on the complex application of bioprotective substances of different origin are used to reduce the intake and accumulation of xenobiotics, to normalize the physiological state of animals and to obtain safe products. It is necessary to observe certain principles ensuring compatibility of components, a wide range of bioprotective action, efficiency and safety at their use in developing the compositions of such sorption-detoxifying complexes. The article substantiates the criteria that should be followed in creating sorption-detoxifying complexes and presents groups of drugs with different mechanisms of action (sorbents, antioxidants, immunomodulators, adaptogens and other biologically active substances) for inclusion in the formulations of combined compositions.


mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Timothy A. Johnson ◽  
Torey Looft ◽  
Andrew J. Severin ◽  
Darrell O. Bayles ◽  
Daniel J. Nasko ◽  
...  

ABSTRACT Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome) and phage population dynamics (fecal dsDNA viromes). Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences) and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the control and carbadox communities were distinct 2 days after carbadox introduction. This effect was driven by carbadox-associated lower expression of FIGfams (n = 66) related to microbial respiration, carbohydrate utilization, and RNA metabolism (q < 0.1), suggesting bacteriostatic or bactericidal effects within certain populations. Interestingly, carbadox treatment caused greater expression of FIGfams related to all stages of the phage lytic cycle 2 days following the introduction of carbadox (q ≤0.07), suggesting the carbadox-mediated induction of prophages and phage DNA recombination. These effects were diminished by 7 days of continuous carbadox in the feed, suggesting an acute impact. Additionally, the viromes included a few genes that encoded resistance to tetracycline, aminoglycoside, and beta-lactam antibiotics but these did not change in frequency over time or with treatment. The results show decreased bacterial growth and metabolism, prophage induction, and potential transduction of bacterial fitness genes in swine gut bacterial communities as a result of carbadox administration. IMPORTANCE FDA regulations on agricultural antibiotic use have focused on antibiotics that are important for human medicine. Carbadox is an antibiotic not used in humans but frequently used on U.S. pig farms. It is important to study possible side effects of carbadox use because it has been shown to promote bacterial evolution, which could indirectly impact antibiotic resistance in bacteria of clinical importance. Interestingly, the present study shows greater prophage gene expression in feces from carbadox-fed animals than in feces from nonmedicated animals 2 days after the initiation of in-feed carbadox treatment. Importantly, the phage genetic material isolated in this study contained genes that could provide resistance to antibiotics that are important in human medicine, indicating that human-relevant antibiotic resistance genes are mobile between bacteria via phages. This study highlights the collateral effects of antibiotics and demonstrates the need to consider diverse antibiotic effects whenever antibiotics are being used or new regulations are considered. FDA regulations on agricultural antibiotic use have focused on antibiotics that are important for human medicine. Carbadox is an antibiotic not used in humans but frequently used on U.S. pig farms. It is important to study possible side effects of carbadox use because it has been shown to promote bacterial evolution, which could indirectly impact antibiotic resistance in bacteria of clinical importance. Interestingly, the present study shows greater prophage gene expression in feces from carbadox-fed animals than in feces from nonmedicated animals 2 days after the initiation of in-feed carbadox treatment. Importantly, the phage genetic material isolated in this study contained genes that could provide resistance to antibiotics that are important in human medicine, indicating that human-relevant antibiotic resistance genes are mobile between bacteria via phages. This study highlights the collateral effects of antibiotics and demonstrates the need to consider diverse antibiotic effects whenever antibiotics are being used or new regulations are considered.


2006 ◽  
Vol 96 (3) ◽  
pp. 264-268
Author(s):  
Charles R. Fikar ◽  
Brigitte Delinois

An updated selection of high-quality Internet resources related to wound and ulcer care is presented. Of potential use to the podiatric medical practitioner, educator, resident, and student, some Web sites that cover hyperbaric medicine, antibiotic use, and wound and ulcer prevention are also included. These Web sites have been evaluated on the basis of their potential to enhance the practice of podiatric medicine, in addition to contributing to the educational process. Readers who require a quick reference source to wound and ulcer care may find this report useful. (J Am Podiatr Med Assoc 96(3): 264–268, 2006)


2018 ◽  
Vol 11 (12) ◽  
pp. 671-675
Author(s):  
Patrick Liddicoat

Bad news constitutes any piece of information with the potential to have a negative impact on a person’s life. During their career, all doctors will break bad news on a regular basis, and the manner in which this news is broken can deeply influence how much patients understand and then react. This article will explore the importance of breaking bad news, and outline a selection of techniques to help achieve more effective and empathetic communication.


2021 ◽  
pp. 2941-2946
Author(s):  
Nubwa Daniel ◽  
Kefas David Malgwi ◽  
Bukar Umaru ◽  
Isaac John Omeh ◽  
Ladi Sanya

Background and Aim: Veterinary antibiotics are widely used to treat bacterial diseases in various species of animals. However, despite the importance of these chemotherapeutic agents, their indiscriminate or extensive use can pose dangers to the animals or humans that consume edible tissues from animals contaminated with antibiotic residues. Therefore, concerns regarding their appropriate and judicious use in animals are of public health significance. This is because of the tendencies of developing resistance to targeted microbes and the ability of the parent compound or its metabolites to persist as residues in the animal tissues. This study aimed to determine the frequency and pattern of antibiotic usage and ascertain the level of awareness of clinicians on the judicious use of antibiotics at the University of Maiduguri Veterinary Teaching Hospital, Maiduguri, Borno State, Nigeria. Materials and Methods: Data related to the administration of antibiotics in all species of animals presented for treatment from January 2009 to December 2018 were obtained from the hospital archives, with permission from the office of the hospital directorate. The diseases, hospital units, antibiotics used, and years were parameters that were recorded for each case. Furthermore, 47 questionnaires were administered to clinicians who render services to the hospital. Results: A total of 63.9% of all cases brought to the hospital within the 10 years under study were infectious, and as such, were treated with antibiotics. The highest recorded use of antibiotics was observed in the poultry unit (38.4%), followed by the large animal unit (24.1%), with the lowest used recorded in the ambulatory unit (9.3%). Furthermore, regarding the antibiotics used, oxytetracycline had the highest occurrence (55%), followed by penicillin-streptomycin combination (12.2%), with the lowest being metronidazole (0.30%). The highest number of cases treated with antibiotics was recorded in 2018 (22.5%), and the lowest was recorded in 2014 (1.3%). Regarding the questionnaire administered to the clinicians, 78.7% of the respondents preferred oxytetracycline as their drug of choice, whereas only 2.1%, 4.3%, 2.1%, and 4.3% preferred amoxicillin, penicillin, streptomycin, and penicillin-streptomycin, respectively. Moreover, 65.9% of the respondents used a particular antibiotic because of its availability at the hospital, 8.5% because of cost, and 27.7% because of clinician preference. Furthermore, 74.5% of the clinicians offered palliative intervention while awaiting laboratory reports, whereas 8.5% treated the animals without requesting laboratory analyses. Conclusion: In this study, oxytetracycline was found to be the most used antibiotic for treating infectious diseases at the hospital because of its availability. The observed pattern appeared in the following order of frequency: Oxytetracycline, penicillin-streptomycin combination, neomycin, erythromycin, amoxicillin, tylosin, streptomycin, and gentamicin with metronidazole being the least frequent. There might also be antibiotic resistance, which requires a change to another antibiotic because of the lack of response to the initial antibiotic. Non-judicious antibiotic use can also have a negative impact on public health because of the development of multidrug-resistant "superbugs" and the problem of drug residue.


2020 ◽  
Author(s):  
Chengliang Huang ◽  
Meizhang Li ◽  
Ben Liu ◽  
Huanbo Zhu ◽  
Qun Dai ◽  
...  

Abstract Background: Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet.Methods: A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included.Results: At the phylum level, patients who had enriched abundance in Firmicutes and Verrucomicrobia almost universally had better response from ICIs, whereas those who were enriched in Proteobacteria universally presented with unfavorable outcome. Mixed correlations were observed for Bacteroidetes in relating to treatment response. Regarding the AEs, Firmicutes correlated to higher incidence whereas Bacteroidetes were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of “ICI-favoring” gut microbiome (P = 0.0476).Conclusions: Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.


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