Geraniol, a Potential Alternative to Antibiotics for Bovine Mastitis Treatment Without Disturbing the Host Microbial Community, Does Not Lead to Drug Residues or Induce Drug Resistance

Abstract BackgroundMastitis is one of the important diseases of the dairy cow. Currently, mastitis treatment in dairy cows is mainly based on antibiotics. However, the use of antibiotics causes adverse effects, including drug resistance, drug residues, host-microbiome destruction, and environmental pollution. Geraniol, extracted from Fructus Tsaoko, has demonstrated good antibacterial activity in mouse model. Geraniol and antibiotics were used to treat cows with clinical mastitis to test this possibility of geraniol as a potential alternative to antibiotics for bovine mastitis treatment. The effectiveness of treatment, improvement in inflammatory factors, the influence on microbiome, presence of drug residues, and induction of drug resistance were compared and analyzed.ResultsGeraniol demonstrated a better therapeutic rate than antibiotics on clinical mastitis of cows, with a longer course of treatment. Antibiotics and geraniol significantly reduced the abundance of pathogenic bacteria and restored the microbial community in milk. Meanwhile, geraniol increased the abundance of probiotics in milk. Interestingly, geraniol did not destroy the gut microbial community of cows, whereas antibiotics significantly reduced the diversity and destroyed the community structure of the gut microbiome in cows. Conversely, geraniol increased the diversity of the gut microbiome. Besides, no geraniol residue was detected in the milk four days after treatment discontinuation. However, antibiotic residues were detected in milk at the 7th day after drug withdrawal. In vitro experiments revealed that geraniol did not induce drug resistance in the Escherichia coli strain ATCC25922 after 120 generations of culturing, while antibiotics induced resistance after 10 generations. ConclusionsOur results suggest that geraniol has antibacterial and anti-inflammatory effects similar to antibiotics. Additionally, it retains the structure of the host-microbial community and does not lead to drug residues or induce drug resistance. Therefore, geraniol can be a potential substitute for antibiotics to treat mastitis and be widely used in the dairy industry.

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In vitro antimicrobial activity of mexican plants on bovine mastitis bacteria: preliminary studies

Bioscience Journal ◽

10.14393/bj-v36n1a2020-42137 ◽

2020 ◽

Vol 36 (1) ◽

Author(s):

Mariana Macías Alonso ◽

Julio C. López Salazar ◽

Soraya Osegueda Robles ◽

Iván Córdova Guerrero ◽

Fernanda Ledezma García ◽

...

Keyword(s):

Antimicrobial Activity ◽

Low Cost ◽

Bovine Mastitis ◽

Ethanolic Extract ◽

Clinical Mastitis ◽

Potential Candidate ◽

Salmonella Spp ◽

Shigella Spp ◽

In Vitro Antibacterial Activity

The present study aimed to evaluate the efficacy of traditionally used antibacterial plants (Euphorbia prostrata, Schinus molle, Brickellia veronicaefolia and Lepidium virginicum) in Santa Rosa Range in Guanajuato against major mastitis-causing pathogens. The selected plants were phytochemically screened for alkaloids, flavonoids, polyphenols, saponins, anthraquinone, cardiac glycosides, steroids and terpenoids. Moreover, to achieve the main purpose of the present research, extracts of selected plants were tested for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Shigella spp., Bacillus subtilis, Clavibacter spp., Proteus vulgaris and Salmonella spp. All these bacterial were isolated from clinical mastitis in dairy cows. The results indicated that the ethanolic extract of the aerial part of L. virginicum exhibited the strongest antimicrobial activity, and it could be potential candidate specie for the development of novel veterinary drugs with low cost and fewer side effects.

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Food Starch Structure Impacts Gut Microbiome Composition

mSphere ◽

10.1128/msphere.00086-18 ◽

2018 ◽

Vol 3 (3) ◽

Cited By ~ 44

Author(s):

Frederick J. Warren ◽

Naoki M. Fukuma ◽

Deirdre Mikkelsen ◽

Bernadine M. Flanagan ◽

Barbara A. Williams ◽

...

Keyword(s):

Small Intestine ◽

Microbial Community ◽

Gut Microbiome ◽

Nutritive Value ◽

Human Diet ◽

Fermentation Products ◽

Microbiome Composition ◽

Starch Fermentation ◽

Starch Structure

ABSTRACT Starch is a major source of energy in the human diet and is consumed in diverse forms. Resistant starch (RS) escapes small intestinal digestion and is fermented in the colon by the resident microbiota, with beneficial impacts on colonic function and host health, but the impacts of the micro- and nanoscale structure of different physical forms of food starch on the broader microbial community have not been described previously. Here, we use a porcine in vitro fermentation model to establish that starch structure dramatically impacts microbiome composition, including the key amylolytic species, and markedly alters both digestion kinetics and fermentation outcomes. We show that three characteristic food forms of starch that survive digestion in the small intestine each give rise to substantial and distinct changes in the microbiome and in fermentation products. Our results highlight the complexity of starch fermentation processes and indicate that not all forms of RS in foods are degraded or fermented in the same way. This work points the way for the design of RS with tailored degradation by defined microbial communities, informed by an understanding of how substrate structure influences the gut microbiome, to improve nutritive value and/or health benefits. IMPORTANCE Dietary starch is a major component in the human diet. A proportion of the starch in our diet escapes digestion in the small intestine and is fermented in the colon. In this study, we use a model of the colon, seeded with porcine feces, in which we investigate the fermentation of a variety of starches with structures typical of those found in foods. We show that the microbial community changes over time in our model colon are highly dependent on the structure of the substrate and how accessible the starch is to colonic microbes. These findings have important implications for how we classify starches reaching the colon and for the design of foods with improved nutritional properties.

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Characteristics ofEscherichia coliIsolated from Bovine Mastitis Exposed to Subminimum Inhibitory Concentrations of Cefalotin or Ceftazidime

BioMed Research International ◽

10.1155/2018/4301628 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Gang Liu ◽

Laidi Ding ◽

Bo Han ◽

Sofie Piepers ◽

S. Ali Naqvi ◽

...

Keyword(s):

Escherichia Coli ◽

Antimicrobial Resistance ◽

Morphological Changes ◽

Bovine Mastitis ◽

Clinical Mastitis ◽

Powdered Infant Formula ◽

Formula Milk ◽

Extended Spectrum Beta Lactamase ◽

E Coli

Escherichia coliis a major udder pathogen causing clinical mastitis in dairy cattle and its heat stable endotoxin in powdered infant formula milk is a potential risk factor in neonatal infections. Cephalosporins are frequently used for treatment of mastitis caused by mastitis; however, use of these antimicrobials may induce antimicrobial resistance inE. coli. The objective of this study was to explore thein vitroeffect of subminimum inhibitory concentrations (sub-MIC) of cefalotin (CF) and ceftazidime (CAZ) on the morphology, antimicrobial resistance, and endotoxin releasing characteristics of 3E. coliisolates recovered from bovine clinical mastitis. The parentE. coliisolates, which were susceptible to CF and CAZ, were exposed to CF or CAZ separately at sub-MIC levels to produce 9 generations of induced isolates. Colonies of the CAZ-induced isolates from all 3 parentE. coliwere smaller on blood agar and the bacteria became filamentous, whereas the CF-induced isolates did not demonstrate prominent morphological changes. After induction by CF or CAZ, many induced isolates showed resistance to cefoxitin, CAZ, CF, kanamycin, ampicillin, and amoxicillin/clavulanic acid while their parent isolates were susceptible to these antimicrobials. Notably, 5 CAZ-induced isolates from the same parent isolate were found to produce extended-spectrum beta-lactamase (ESBL) though none of the tested ESBL related genes could be detected. All CAZ-induced isolates released more endotoxin with a higher release rate, whereas endotoxin release of CF-inducedE. coliisolates was not different from parent isolates. The exposure of cephalosporins at sub-MIC levels induced resistantEscherichia coli.We inferred that cephalosporins, especially CAZ, should be used prudently for treatment of clinicalE. colimastitis.

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Transcriptome Analysis of The Inflammatory Responses of Bovine Mammary Epithelial Cells: Exploring Immunomodulatory Target Genes for Bovine Mastitis

Pathogens ◽

10.3390/pathogens9030200 ◽

2020 ◽

Vol 9 (3) ◽

pp. 200 ◽

Cited By ~ 3

Author(s):

Md. Aminul Islam ◽

Michihiro Takagi ◽

Kohtaro Fukuyama ◽

Ryoya Komatsu ◽

Leonardo Albarracin ◽

...

Keyword(s):

Dairy Cows ◽

Bacterial Infections ◽

Target Genes ◽

Inflammatory Responses ◽

Bovine Mastitis ◽

Immune Defense ◽

Mammary Epithelial ◽

Inflammatory Factors ◽

Cytokines And Chemokines

Bovine mastitis is the inflammatory reaction of the mammary gland and is commonly caused by bacterial infections in high-yielding dairy cows. The detailed investigation of the immunotranscriptomic response of bovine mammary epithelial (BME) cells to pattern recognition receptors (PRRs) activation by microbial-associated molecular patterns (MAMPs) can be of great importance for understanding the innate immune defense mechanisms, and for exploring the immunomodulatory candidate genes. In this work, we investigated the transcriptome modifications of BME cells after the in vitro stimulation with Escherichia coli derived lipopolysaccharide (LPS) and heat-killed Staphylococcus aureus JE2 and S. aureus SA003. In addition, the effect of Pam3CSK4 (a synthetic triacylated lipopeptide that activates Toll-like receptor 2 (TLR2)), and the intracellular chemotactic protein cyclophilin A (CyPA), which is secreted by BME cells during mastitis, in the expression changes of selected cytokines and chemokines were evaluated by qPCR. Microarray analysis identified 447, 465 and 520 differentially expressed genes (DEGs) in the BME cells after LPS, S. aureus JE2 and S. aureus SA003 stimulation, respectively. A major differential response in the inflammatory gene expression was noticed between the stimulation of LPS and S. aureus strains. Unlike the S. aureus strains, LPS stimulation resulted in significant upregulation of CCL2, CXCL2, CXCL3, CXCL8, IL1α and IL1β, which were confirmed by qPCR analysis. Pam3CSK4 was not able to induce significant changes in the expression of cytokines and chemokines in challenged BME cells. The exogenous CyPA administration was able to upregulate CXCL2, CXCL3, CXCL8, IL1α and IL1β expression in BME cells indicating its ability to promote inflammation. The identification of transcriptional markers of mastitis specific for individual inflammatory factors such as LPS, Pam3CSK4 or CyPA, which can be evaluated in vitro in BME cells, may enable the development of novel diagnostics and/or immunomodulatory treatments, providing new tools for the effective management of mastitis in dairy cows. The results of this work are an advance in this regard.

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Design, Synthesis, and Biological Activity of Novel Myricetin Derivatives Containing Amide, Thioether, and 1,3,4-Thiadiazole Moieties

Molecules ◽

10.3390/molecules23123132 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3132 ◽

Cited By ~ 5

Author(s):

Xianghui Ruan ◽

Cheng Zhang ◽

Shichun Jiang ◽

Tao Guo ◽

Rongjiao Xia ◽

...

Keyword(s):

Antibacterial Activity ◽

Pathogenic Bacteria ◽

Antibacterial Activities ◽

Xanthomonas Oryzae ◽

Design Synthesis ◽

Antiviral Activities ◽

Potential Alternative ◽

Better Than

A series of myricetin derivatives containing amide, thioether, and 1,3,4-thiadiazole moieties were designed and synthesized, and their antiviral and antibacterial activities were assessed. The bioassays showed that all the title compounds exhibited potent in vitro antibacterial activities against Xanthomonas citri (Xac), Ralstonia solanacearum (Rs), and Xanthomonas oryzae pv. Oryzae (Xoo). In particular, the compounds 5a, 5f, 5g, 5h, 5i, and 5l, with EC50 values of 11.5–27.3 μg/mL, showed potent antibacterial activity against Xac that was better than the commercial bactericides Bismerthiazol (34.7 μg/mL) and Thiodiazole copper (41.1% μg/mL). Moreover, the in vivo antiviral activities against tobacco mosaic virus (TMV) of the target compounds were also tested. Among these compounds, the curative, protection, and inactivation activities of 5g were 49.9, 52.9, and 73.3%, respectively, which were better than that of the commercial antiviral Ribavirin (40.6, 51.1, and 71.1%, respectively). This study demonstrates that myricetin derivatives bearing amide, thioether, and 1,3,4-thiadiazole moieties can serve as potential alternative templates for the development of novel, highly efficient inhibitors against plant pathogenic bacteria and viruses.

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Influence of multi-species biofilm formed in vitro from different environmental samples on the drug-resistance traits of resident bacteria

Bangladesh Journal of Microbiology ◽

10.3329/bjm.v35i2.42639 ◽

2019 ◽

Vol 35 (2) ◽

pp. 108-114

Author(s):

Saurab Kishore Munshi ◽

Tamanna Haque ◽

Rashed Noor

Keyword(s):

Waste Water ◽

Drug Resistance ◽

Pathogenic Bacteria ◽

Agricultural Field ◽

Domestic Waste ◽

Acquired Drug Resistance ◽

Pharmaceutical Waste ◽

Extended Frequency ◽

Enriched Environments

Present study was designed to investigate whether the formation of multi-species biofilm impart any effect on the enhancement of the antibiotic resistance of the planktonic cells residing in the general nutrient enriched environments. In this regard, surface water of pond, mud from agricultural field, pharmaceutical waste waters, municipal waste water, hospital waste water and the domestic waste samples were collected and were induced to form an in vitro multi-species biofilm. All samples were found to contain huge array of pathogenic bacteria. The pathogenic isolates both from the bulk samples and their corresponding biofilms were subjected to antibiogram assay using 13 commonly used antibiotics. An extended frequency of drug resistance was observed in case of biofilm isolates. The findings of present study revealed that a number of bacterial isolates which showed sensitivity towards antibiotics, acquired drug-resistance when they were isolated from biofilms. Bangladesh J Microbiol, Volume 35 Number 2 December 2018, pp 108-114

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Multidrug Therapy and Evolution of Antibiotic Resistance: When Order Matters

Applied and Environmental Microbiology ◽

10.1128/aem.01078-12 ◽

2012 ◽

Vol 78 (17) ◽

pp. 6137-6142 ◽

Cited By ~ 20

Author(s):

Gabriel G. Perron ◽

Sergey Kryazhimskiy ◽

Daniel P. Rice ◽

Angus Buckling

Keyword(s):

Drug Resistance ◽

Multidrug Resistance ◽

Pathogenic Bacteria ◽

Health Workers ◽

Multiple Drug Resistance ◽

Sequential Therapy ◽

Resistant Bacteria ◽

Multiple Drug ◽

Multidrug Therapy

ABSTRACTThe evolution of drug resistance among pathogenic bacteria has led public health workers to rely increasingly on multidrug therapy to treat infections. Here, we compare the efficacy of combination therapy (i.e., using two antibiotics simultaneously) and sequential therapy (i.e., switching two antibiotics) in minimizing the evolution of multidrug resistance. Usingin vitroexperiments, we show that the sequential use of two antibiotics againstPseudomonas aeruginosacan slow down the evolution of multiple-drug resistance when the two antibiotics are used in a specific order. A simple population dynamics model reveals that using an antibiotic associated with high costs of resistance first minimizes the chance of multidrug resistance evolution during sequential therapy under limited mutation supply rate. As well as presenting a novel approach to multidrug therapy, this work shows that costs of resistance not only influences the persistence of antibiotic-resistant bacteria but also plays an important role in the emergence of resistance.

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Antimicrobial and antibiofilm potentials of cinnamon oil and silver nanoparticles against Streptococcus agalactiae isolated from bovine mastitis: new avenues for countering resistance

BMC Veterinary Research ◽

10.1186/s12917-021-02842-9 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Norhan K. Abd El-Aziz ◽

Ahmed M. Ammar ◽

El-sayed Y. M. El-Naenaeey ◽

Hend M. El Damaty ◽

Asmaa A. Elazazy ◽

...

Keyword(s):

Silver Nanoparticles ◽

Streptococcus Agalactiae ◽

Quantitative Polymerase Chain Reaction ◽

Bovine Mastitis ◽

Dairy Farms ◽

Clinical Mastitis ◽

In Vivo Studies ◽

Cinnamon Oil

Abstract Background Streptococcus agalactiae (S. agalactiae) is a contagious pathogen of bovine mastitis. It has financial implications for the dairy cattle industry in certain areas of the world. Since antimicrobial resistance increases in dairy farms, natural antimicrobials from herbal origins and nanoparticles have been given more attention as an alternative therapy. Hence, this study reported the antimicrobial and antibiofilm potentials of cinnamon oil, silver nanoparticles (AgNPs), and their combination against multidrug-resistant (MDR) S. agalactiae recovered from clinical bovine mastitis in Egypt. Results Our findings revealed that 73% (146/200) of the examined milk samples collected from dairy cows with clinical mastitis were infected with Streptococci species. Of these, 9.59% (14/146) were identified as S. agalactiae and categorized as MDR. S. agalactiae isolates expressed four virulence genes (Hyl, cylE, scpB, and lmb) and demonstrated an ability to produce biofilms. Cinnamon oil showed high antimicrobial (MICs ≤0.063 μg /mL) and antibiofilm (MBIC50 = 4 μg/mL) potentials against planktonic and biofilms of S. agalactiae isolates, respectively. However, AgNPs showed reasonable antimicrobial (MICs ≤16 μg/mL) and relatively low antibiofilm (MBIC50 = 64 μg/mL) activities against screened isolates. Synergistic antimicrobial or additive antibiofilm interactions of cinnamon oil combined with AgNPs were reported for the first time. Scanning electron microscope (SEM) analysis revealed that biofilms of S. agalactiae isolates treated with cinnamon oil were more seriously damaged than observed in AgNPs cinnamon oil combination. Moreover, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) showed that cinnamon oil exerted a remarkable down-regulation of pili biosynthesis genes (pilA and pilB) and their regulator (rogB) against S. agalactiae biofilms, meanwhile the AgNPs cinnamon oil combination demonstrated a lower efficacy. Conclusions This is an in vitro preliminary approach that documented the antibiofilm potential of cinnamon oil and the inhibitory activity of cinnamon oil and its combination with AgNPs against MDR S. agalactiae recovered from clinical mastitis. Further in vivo studies should be carried out in animal models to provide evidence of concept for implementing these alternative candidates in the treatment of dairy farms infected by streptococcal mastitis in the future.

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Bovine mastitis may be associated with the deprivation of gut Lactobacillus

Beneficial Microbes ◽

10.3920/bm2015.0048 ◽

2016 ◽

Vol 7 (1) ◽

pp. 95-102 ◽

Cited By ~ 10

Author(s):

C. Ma ◽

J. Zhao ◽

X. Xi ◽

J. Ding ◽

H. Wang ◽

...

Keyword(s):

Clinical Trials ◽

Microbial Community ◽

Somatic Cell Count ◽

Close Association ◽

Bovine Mastitis ◽

Clinical Mastitis ◽

Lactobacillus Species ◽

General Increase ◽

Community Changes ◽

Mastitis Pathogens

Bovine mastitis is an economical important microbial disease in dairy industry. Some recent human clinical trials have shown that oral probiotics supplementation could effectively control clinical mastitis, suggesting that the mechanism of mastitis protection might be achieved via the host gut microbiota. We aimed to test our hypothesis that bovine mastitis was related to changes in both the mammary and gut microbial profiles. By quantitative PCR, the milk and faecal microbial profiles of cows with low (<3×105 cells/ml) and high (>1×106 cells/ml) somatic cell count (SCC) were compared. Firstly, we observed drastic differences in both the milk and faecal microbial compositions at genus and Lactobacillus-species levels between the two groups. Secondly, the pattern of faecal microbial community changes of mastitis cows was similar to that of the milk, characterised by a general increase in the mastitis pathogens (Enterococcus, Streptococcus and Staphylococcus) and deprivation of Lactobacillus and its members (L. salivarius, L. sakei, L. ruminis, L. delbrueckii, L. buchneri, and L. acidophilus). Thirdly, only the faecal lactobacilli, but not bifidobacteria correlated with the milk microbial communities and SCC. Our data together hint to a close association between bovine mastitis, the host gut and milk microbiota.

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A New Concept of Enhancing the Efficacy of Antimicrobial Therapy of Pyo-Inflammatory Diseases in Children

Galician Medical Journal ◽

10.21802/gmj.2016.3.6 ◽

2016 ◽

Vol 23 (3) ◽

Author(s):

V. B. Davydenko ◽

M. M. Mishyna ◽

V. V. Myasoedov ◽

Yu. V. Pashchenko ◽

S. Yu. Shtyker ◽

...

Keyword(s):

Drug Resistance ◽

Virulence Factors ◽

Antimicrobial Therapy ◽

Pathogenic Bacteria ◽

Antimicrobial Agents ◽

Inflammatory Diseases ◽

Causative Agents ◽

Spread Of Infection ◽

High Degree

Pyo-inflammatory diseases are quite common among various surgical diseases in children. Etiotropic antimicrobial therapy of these conditions is of primary importance. Modern pathogenic bacteria possess a high degree of drug resistance to antimicrobials, which significantly reduces the effectiveness of treatment and contributes to the spread of infection and the development of pyo-inflammatory complications.The objective of the research was to study peculiar properties of virulence factors production by S. aureus within 24 hours as well as to determine on this basis the directions of improving the efficiency of antimicrobial therapy of pyo-inflammatory diseases in children.Materials and methods. There were conducted in vitro experimental microbiological studies concerning the study of the daily dynamics of virulence factors of causative agents of purulent-inflammatory diseases in children. The materials for the study were as follows: wound tissues, purulent exudate, dressings and suture material, catheters and drainage elements.Results. Microbiological studies revealed that drug resistance of pathogenic microorganisms originates from the production of various factors of bacterial aggression including the formation of biofilms. The study showed that the level of production of virulence factors and the sensitivity of S. aureus to antimicrobial agents were not constant over the day. Recorded peaks of increasing adhesive activity, teichoic acids content, production of planktonic cells and formation of dense biofilms by S. aureus depended on the time of administration of antimicrobials and maximum concentration of the medication in an organism.Conclusions. The regularity observed allowed us to develop a new concept to increase the efficiency of treatment of pyo-inflammatory diseases in children by means of change in the time for administration of antimicrobial agents during the day so that the period of maximum action would coincide with periods of minimal drug resistance of pathogens. This will allow us to significantly improve the effectiveness of antimicrobial therapy without increasing doses of medications that are administered.

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