scholarly journals Developing Actinobacterial Endophytes as Biocontrol Products for Fusarium pseudograminearum in Wheat

2021 ◽  
Vol 9 ◽  
Author(s):  
Cathryn A. O’Sullivan ◽  
Margaret M. Roper ◽  
Cindy A. Myers ◽  
Louise F. Thatcher
Keyword(s):  
Management Strategies ◽  
Agar Plate ◽  
Treatment Strategies ◽  
Crown Rot ◽  
Yield Losses ◽  
Disease Symptoms ◽  
Fusarium Pseudograminearum ◽  
Unsterilized Soil ◽  
Novel Treatment Strategies

Crown rot of wheat, caused by Fusarium pseudograminearum, results in millions of dollars of yield losses globally each year. Management strategies to control crown rot are limited and there are concerns about development of fungicide resistance so novel treatment strategies are desirable. A collection of endophytic Actinobacteria was screened for their ability to suppress the growth of F. pseudograminearum and the development of crown rot symptoms in wheat with the aim of identifying candidates that can be developed into biocontrol products. The ability of the Actinobacteria isolates to suppress the growth of three different F. pseudograminearum strains in vitro was assessed using agar-plate competition assays. Soil-free seedling assays were used to screen for suppression of development of early disease symptoms in the susceptible wheat (Triticum aestivum) cv. Tamaroi. Four of the isolates were tested in a glasshouse pot experiment to assess their ability to decrease disease symptoms and prevent yield losses in wheat cv. Tamaroi grown to maturity in an unsterilized soil. The screening of 53 isolates identified two Streptomyces isolates, MH71 and MH243, with very strong antifungal activity against F. pseudograminearum strains in agar-plate competition and seedling assays. In the glasshouse pot trial, plants treated with seed coatings of either MH71 or MH243 had > 24% lower disease severity than control plants infected with F. pseudograminearum. These two cultures show potential for development as biocontrol products because they are easy to culture, grow on relatively inexpensive media, produce highly durable spores and can be delivered to plants as a seed coat.

scholarly journals Molecular mechanisms underpinning sarcomas and implications for current and future therapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Victoria Damerell ◽  
Michael S. Pepper ◽  
Sharon Prince
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Treatment Strategies ◽  
Mesenchymal Transition ◽  
Mesenchymal To Epithelial Transition ◽  
Cells Of Origin ◽  
Novel Treatment Strategies ◽  
Future Therapy

AbstractSarcomas are complex mesenchymal neoplasms with a poor prognosis. Their clinical management is highly challenging due to their heterogeneity and insensitivity to current treatments. Although there have been advances in understanding specific genomic alterations and genetic mutations driving sarcomagenesis, the underlying molecular mechanisms, which are likely to be unique for each sarcoma subtype, are not fully understood. This is in part due to a lack of consensus on the cells of origin, but there is now mounting evidence that they originate from mesenchymal stromal/stem cells (MSCs). To identify novel treatment strategies for sarcomas, research in recent years has adopted a mechanism-based search for molecular markers for targeted therapy which has included recapitulating sarcomagenesis using in vitro and in vivo MSC models. This review provides a comprehensive up to date overview of the molecular mechanisms that underpin sarcomagenesis, the contribution of MSCs to modelling sarcomagenesis in vivo, as well as novel topics such as the role of epithelial-to-mesenchymal-transition (EMT)/mesenchymal-to-epithelial-transition (MET) plasticity, exosomes, and microRNAs in sarcomagenesis. It also reviews current therapeutic options including ongoing pre-clinical and clinical studies for targeted sarcoma therapy and discusses new therapeutic avenues such as targeting recently identified molecular pathways and key transcription factors.

scholarly journals Antimicrobial activity of a novel bioengineered honey against non-typeable Haemophilus influenzae biofilms: an in vitro study

2018 ◽  
Vol 71 (6) ◽  
pp. 554-558 ◽  
Author(s):  
Rachel S Newby ◽  
Matthew Dryden ◽  
Raymond N Allan ◽  
Rami J Salib
Keyword(s):  
Haemophilus Influenzae ◽  
Treatment Strategies ◽  
In Vitro Study ◽  
Opportunistic Pathogen ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Novel Treatment ◽  
Novel Treatment Strategies

The opportunistic pathogen non-typeable Haemophilus influenzae (NTHi) plays an important role in many chronic respiratory diseases including otitis media, chronic rhinosinusitis, cystic fibrosis and chronic obstructive pulmonary disease. Biofilm formation has been implicated in NTHi colonisation, persistence of infection and recalcitrance towards antimicrobials. There is therefore a pressing need for the development of novel treatment strategies that are effective against NTHi biofilm-associated diseases. SurgihoneyRO is a honey-based product that has been bioengineered to enable the slow release of H2O2, a reactive oxygen species to which H. influenzae is susceptible. Treatment of established NTHi biofilms with SurgihoneyRO significantly reduced biofilm viability through enhanced H2O2 production and was shown to be more effective than the conventional antibiotic co-amoxiclav.

scholarly journals Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study

2020 ◽  
Author(s):  
Jeffrey D Klausner ◽  
Claire C Bristow ◽  
Olusegun O Soge ◽  
Akbar Shahkolahi ◽  
Toni Waymer ◽  
...  
Keyword(s):  
Single Dose ◽  
Clinical Study ◽  
Scale Up ◽  
Treatment Strategies ◽  
Prospective Clinical Study ◽  
Dose Oral ◽  
Novel Treatment Strategies ◽  
Oral Ciprofloxacin ◽  
Culture Positive

Abstract Background Novel treatment strategies to slow the continued emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae are urgently needed. A molecular assay that predicts in vitro ciprofloxacin susceptibility is now available but has not been systematically studied in human infections. Methods Using a genotypic polymerase chain reaction assay to determine the status of the N. gonorrhoeae gyrase subunit A serine 91 codon, we conducted a multisite prospective clinical study of the efficacy of a single oral dose of ciprofloxacin 500 mg in patients with culture-positive gonorrhea. Follow-up specimens for culture were collected to determine microbiological cure 5–10 days post-treatment. Results Of the 106 subjects possessing culture-positive infections with wild-type gyrA serine N. gonorrhoeae genotype, the efficacy of single-dose oral ciprofloxacin treatment in the per-protocol population was 100% (95% 1-sided confidence interval, 97.5–100%). Conclusions Resistance-guided treatment of N. gonorrhoeae infections with single-dose oral ciprofloxacin was highly efficacious. The widespread introduction and scale-up of gyrA serine 91 genotyping in N. gonorrhoeae infections could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible. Clinical Trials Registration NCT02961751.

scholarly journals Therapeutic Effects of Curcumin—From Traditional Past to Present and Future Clinical Applications

2019 ◽  
Vol 20 (15) ◽  
pp. 3757 ◽  
Author(s):  
Beatrice Bachmeier ◽  
Dieter Melchart
Keyword(s):  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Scientific Evidence ◽  
Treatment Strategies ◽  
Therapeutic Effects ◽  
Microbial Infection ◽  
Therapeutic Benefits ◽  
Novel Treatment Strategies

The efficacy of the plant-derived polyphenol curcumin, in various aspects of health and wellbeing, is matter of public interest. An internet search of the term “Curcumin” displays about 12 million hits. Among the multitudinous information presented on partly doubtful websites, there are reports attracting the reader with promises ranging from eternal youth to cures for incurable diseases. Unfortunately, many of these reports are not based on scientific evidence, but they feed the desideratum of the reader for a “miracle cure”. This circumstance makes it very difficult for researchers, who work in a scientifically sound and evidence-based manner on the therapeutic benefits (or side effects) of curcumin, to demarcate their results from sensational reports that circulate in the web and in other media. This is only one of many obstacles making it difficult to pave curcumin’s way into clinical application; others are its nonpatentability and low economic usability. A further impediment comes from scientists who never worked with curcumin or any other natural plant-derived compound in their own labs. They have never tested these compounds in any scientific assay, neither in vitro nor in vivo; however, they claim, in a sometimes polemic manner, that everything that has so far been published on curcumin’s molecular effects is based on artefacts. The here presented Special Issue comprises a collection of five scientifically sound articles and nine reviews reporting on the therapeutic benefits and the molecular mechanisms of curcumin or of chemically modified curcumin in various diseases ranging from malignant tumors to chronic diseases, microbial infection, and even neurodegenerative diseases. The excellent results of the scientific projects that underlie the five original papers give reason to hope that curcumin will be part of novel treatment strategies in the near future—either as monotherapy or in combination with other drugs or therapeutic applications.

scholarly journals Antibiotic collateral sensitivity is contingent on the repeatability of evolution

2017 ◽  
Author(s):  
Daniel Nichol ◽  
Joseph Rutter ◽  
Christopher Bryant ◽  
Andrea M Hujer ◽  
Sai Lek ◽  
...  
Keyword(s):  
Experimental Evolution ◽  
Treatment Strategies ◽  
Therapeutic Benefit ◽  
Cross Resistance ◽  
Health Crisis ◽  
Collateral Sensitivity ◽  
Drug Regimens ◽  
Novel Treatment Strategies ◽  
Increased Susceptibility

AbstractAntibiotic resistance represents a growing health crisis that necessitates the immediate discovery of novel treatment strategies. One such strategy is the identification of collateral sensitivities, wherein evolution under a first drug induces susceptibility to a second. Here, we report that sequential drug regimens derived from in vitro evolution experiments may have overstated therapeutic benefit, predicting a collaterally sensitive response where cross resistance ultimately occurs. We quantify the likelihood of this phenomenon by use of a mathematical model parametrised with combinatorially complete fitness landscapes for Escherichia coli. Through experimental evolution we then verify that a second drug can indeed stochastically exhibit either increased susceptibility or increased resistance when following a first. Genetic divergence is confirmed as the driver of this differential response through targeted and whole genome sequencing. Taken together, these results highlight that the success of evolutionarily-informed therapies is predicated on a rigorous probabilistic understanding of the contingencies that arise during the evolution of drug resistance.

scholarly journals Assessment of Infection by Fusarium pseudograminearum in Wheat Seedling Tissues Using Quantitative PCR and a Visual Discoloration Scale

Plant Disease ◽  
2012 ◽  
Vol 96 (11) ◽  
pp. 1661-1669 ◽  
Author(s):  
Noel L. Knight ◽  
Mark W. Sutherland ◽  
Anke Martin ◽  
Damian J. Herde
Keyword(s):  
Fungal Biomass ◽  
Leaf Sheath ◽  
Crown Rot ◽  
Fungal Colonization ◽  
Seedling Resistance ◽  
Disease Symptoms ◽  
Wheat Genotypes ◽  
Fusarium Pseudograminearum ◽  
Fungal Dna ◽  
Visual Assessments

Assessment among cereal genotypes of relative seedling resistance to the crown rot pathogen Fusarium pseudograminearum has been primarily based on visual discoloration of the leaf sheaths. This study is the first to investigate the relationship between the widely used visual rating of seedling leaf sheath discoloration and the degree of colonization of these tissues by the pathogen, based on quantitative polymerase chain reaction (qPCR) of fungal DNA using primers specific for the translation elongation factor α sequence. Fourteen-day-old seedlings of four hard white spring wheat genotypes which differ in their degree of resistance to the pathogen, based on the expression of visible symptoms, were inoculated using a droplet method and assessed weekly from 7 to 35 days after inoculation (dai) for both discoloration and fungal DNA content per unit of tissue weight. Both visual assessment of disease symptoms and qPCR of fungal biomass indicated significant differences between the partially resistant and susceptible wheat genotypes from 14 dai. Visual discoloration of leaf sheath tissues was strongly correlated with fungal biomass estimated by qPCR in all four genotypes; however, this correlation became weaker with increasing time after inoculation. Significant correlations between these parameters were indicated at 14, 21, and 28 dai whereas, by 35 dai, the correlation was not significant. Evaluation of plants at 14 dai provided a rapid test which gave clear discrimination between lines for both parameters and was the time point of closest correlation between fungal colonization and disease symptoms. Symptom expression at all times following inoculation was accompanied by tissue infection, and at no time was symptomless infection observed under this screening environment. These qPCR results confirm that visual assessments of disease symptoms reflect the extent of tissue colonization by the pathogen in recently colonized tissues and confirm the validity of visual assessments for disease rating in high-throughput screening of breeding materials.

scholarly journals Activity of Aztreonam in Combination with Avibactam, Clavulanate, Relebactam, and Vaborbactam against Multidrug-Resistant Stenotrophomonas maltophilia

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
M. Biagi ◽  
D. Lamm ◽  
K. Meyer ◽  
A. Vialichka ◽  
M. Jurkovic ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Molecular Mechanisms ◽  
Efflux Pump ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Content Type ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Novel Treatment Strategies

ABSTRACT The intrinsic L1 metallo- and L2 serine-β-lactamases in Stenotrophomonas maltophilia make it naturally multidrug resistant and difficult to treat. There is a need to identify novel treatment strategies for this pathogen, especially against isolates resistant to first-line agents. Aztreonam in combination with avibactam has demonstrated potential, although data on other aztreonam–β-lactamase inhibitor (BLI) combinations are lacking. Additionally, molecular mechanisms for reduced susceptibility to these combinations have not been explored. The objectives of this study were to evaluate and compare the in vitro activities and to understand the mechanisms of resistance to aztreonam in combination with avibactam, clavulanate, relebactam, and vaborbactam against S. maltophilia. A panel of 47 clinical S. maltophilia strains nonsusceptible to levofloxacin and/or trimethoprim-sulfamethoxazole were tested against each aztreonam-BLI combination via broth microdilution, and 6 isolates were then evaluated in time-kill analyses. Three isolates with various aztreonam-BLI MICs were subjected to whole-genome sequencing and quantitative reverse transcriptase PCR. Avibactam restored aztreonam susceptibility in 98% of aztreonam-resistant isolates, compared to 61, 71, and 15% with clavulanate, relebactam, and vaborbactam, respectively. The addition of avibactam to aztreonam resulted in a ≥2-log10-CFU/ml decrease at 24 h versus aztreonam alone against 5/6 isolates compared to 1/6 with clavulanate, 4/6 with relebactam, and 2/6 with vaborbactam. Molecular analyses revealed that decreased susceptibility to aztreonam-avibactam was associated with increased expression of genes encoding L1 and L2, as well as the efflux pump (smeABC). Aztreonam-avibactam is the most promising BLI-combination against multidrug-resistant S. maltophilia. Decreased susceptibility may be due to the combination of overexpressed β-lactamases and efflux pumps. Further studies evaluating this combination against S. maltophilia are warranted.

scholarly journals Pathogenesis of Keratinocyte Carcinomas and the Therapeutic Potential of Medicinal Plants and Phytochemicals

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1979
Author(s):  
Andrea Jess Josiah ◽  
Danielle Twilley ◽  
Sreejarani Kesavan Pillai ◽  
Suprakas Sinha Ray ◽  
Namrita Lall
Keyword(s):  
Cell Carcinoma ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
In Vivo Studies ◽  
Contributing Factors ◽  
Alternative Approach ◽  
Transdermal Drug Delivery Systems ◽  
Novel Treatment Strategies

Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.

scholarly journals SAAP-148 Eradicates MRSA Persisters Within Mature Biofilm Models Simulating Prosthetic Joint Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Henk Scheper ◽  
Julia M. Wubbolts ◽  
Joanne A. M. Verhagen ◽  
Adriëtte W. de Visser ◽  
Robert J. P. van der Wal ◽  
...  
Keyword(s):  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Treatment Strategies ◽  
Antibacterial Activities ◽  
Current Treatment ◽  
Log Reduction ◽  
Prosthetic Joint ◽  
Novel Treatment Strategies ◽  
Titanium Aluminium

Prosthetic joint infection (PJI) is a severe complication of arthroplasty. Due to biofilm and persister formation current treatment strategies often fail. Therefore, innovative anti-biofilm and anti-persister agents are urgently needed. Antimicrobial peptides with their broad antibacterial activities may be such candidates. An in vitro model simulating PJI comprising of rifampicin/ciprofloxacin-exposed, mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms on polystyrene plates, titanium/aluminium/niobium disks, and prosthetic joint liners were developed. Bacteria obtained from and residing within these biofilms were exposed to SAAP-148, acyldepsipeptide-4, LL-37, and pexiganan. Microcalorimetry was used to monitor the heat flow by the bacteria in these models. Daily exposure of mature biofilms to rifampicin/ciprofloxacin for 3 days resulted in a 4-log reduction of MRSA. Prolonged antibiotic exposure did not further reduce bacterial counts. Microcalorimetry confirmed the low metabolic activity of these persisters. SAAP-148 and pexiganan, but not LL-37, eliminated the persisters while ADEP4 reduced the number of persisters. SAAP-148 further eradicated persisters within antibiotics-exposed, mature biofilms on the various surfaces. To conclude, antibiotic-exposed, mature MRSA biofilms on various surfaces have been developed as in vitro models for PJI. SAAP-148 is highly effective against persisters obtained from the biofilms as well as within these models. Antibiotics-exposed, mature biofilms on relevant surfaces can be instrumental in the search for novel treatment strategies to combat biofilm-associated infections.

Multi-locus phylogenetic analyses of Colletotrichum gloeosporioides species complex causing crown rot on strawberry in Florida

2021 ◽  
Author(s):  
Michelle Souza Oliveira ◽  
Nan-Yi Wang ◽  
Natalia Peres
Keyword(s):  
Colletotrichum Gloeosporioides ◽  
Phylogenetic Analyses ◽  
Management Strategies ◽  
Morphological Characteristics ◽  
Crown Rot ◽  
Cultivated Plants ◽  
Complex Species ◽  
Colletotrichum Gloeosporioides Species Complex ◽  
Genomic Regions

Colletotrichum gloeosporioides is the causal agent of Colletotrichum crown rot of strawberry in the southern United States. Recent multi-gene studies defined C. gloeosporioides as a complex species comprised of 37 species. In our study, we phylogenetically characterized C. gloeosporioides isolates from strawberry and other non-cultivated plants around strawberry fields. One hundred and fifteen strawberry isolates and 38 isolates from non-cultivated hosts were sequenced for five genomic regions: internal transcribed spacer (ITS), actin (ACT), calmodulin (CAL), chitin synthase (CHS-1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Phylogenetic analysis using the maximum likelihood and Bayesian inference methods, based on partition-specific models, revealed that most of the isolates in Florida (86%) were closely related to C. siamense, whereas 14 isolates were closely related to C. theobromicola (syn. C. fragariae), four isolates were C. fructicola, and three were C. clidemiae. However, only the first three species were pathogenic to strawberry. Morphological characteristics evaluated show that mycelial growth of all species is about 5 mm/day but colony morphology varies by species and incubation conditions. In vitro mating of the isolates demonstrated that C. fructicola is homothallic whereas C. siamense and C. theobromicola isolates are heterothallic. The biological importance of these different Colletotrichum species is currently being investigated to determine whether different management strategies are needed in strawberry production fields.

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