Low Risk Of Resistance Research Articles

Field Evaluation of Fluazinam Fungicide in Dollar Spot Populations Confirmed In Vitro Insensitivity.

Fluazinam, a fungicide widely used in agriculture and turf management, was traditionally thought to pose a low risk of resistance. However, our in vitro sensitivity test conducted in 2021 revealed reduced sensitivity to fluazinam in dollar spot, highlighting the need for more vigilant field monitoring. In 2022 and 2023, we evaluated the field responses of four Clarireedia jacksonii isolates with varying in vitro sensitivity to fluazinam. Fluazinam was used at both a full labeled rate (0.5 oz/1,000 ft2) and a half-rate (0.25 oz/1,000 ft2) to evaluate the effectiveness in isolate-inoculated plots in the field. In 2022, both natural and sensitive isolates showed significantly better control compared to insensitive isolates under both half- and full-rate treatments. However, in 2023, half-rate fluazinam demonstrated limited control under high disease pressure, providing relative disease control of dollar spot less than 45% across all treatments. In contrast, full-rate fluazinam maintained significantly better control of natural and sensitive isolates compared with insensitive isolates. Our results, showing that in vitro insensitivity leads to field insensitivity under inoculated conditions, suggest the development of fluazinam insensitivity in the C. jacksonii population. This highlights the need for judicious use of fluazinam and the establishment of continuous resistance monitoring. Furthermore, the loss of control observed when fluazinam was applied at half-rates under high disease pressure highlights the importance of careful fungicide use.

A BODIPY derivative for PDT/PTT synergistic treatment of bacterial infections

Phototherapeutic antimicrobials, including photodynamic and photothermal antimicrobials, are considered effective alternatives for antibiotic strategy due to their broad-spectrum antibacterial activity and low risk of resistance. Here, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivative containing triphenylamine groups was co-assembled with Pluronic F-127 (F-127) to form nanoparticles (BICF NPs). BICF NPs have excellent photodynamic and photothermal properties and are demonstrated to be effective in inhibiting and disrupting bacterial biofilms, thereby promoting the healing of subcutaneous abscesses. This work provides a new avenue for antibiotic replacement therapy.

Lignin-Based Visible Light-Triggered Nitric Oxide Nanogenerator for Antibacterial Applications.

Nitric oxide (NO) has received growing attention as an effective antibacterial agent with broad-spectrum activity and a low risk of resistance. However, it remains challenging to develop effective, controllable, and biocompatible NO-releasing materials. Here, we report a novel NO nanogenerator (AL-BNN6-PEG) self-assembled by lignin, a UV-absorbing and hydrophobic NO donor (N,N'-disec-butyl-N,N'-dinitroso-1,4-phenylenediamine, BNN6), and PEG-DSPE2000. It was discovered that upon visible light irradiation (450-460 nm), BNN6 can be decomposed by lignin within micellar nanoparticles via a photoinduced electron transfer mechanism in the aqueous medium. Lignin not only served as a sustainable carrier, enhancing the water dispersity of BNN6, but also acted as a biocompatible photosensitizer, triggering BNN6 decomposition with the concomitant release of NO. As a result, the micellar nanoparticles displayed superior antibacterial effects against Gram-negative and Gram-positive bacteria upon visible light illumination. Moreover, MTT assay revealed the negligible cytotoxic effect of the micellar nanoparticles to the mouse fibroblast cells (L929). This research provides more insight into the BNN6 decomposition mechanism and demonstrates a straightforward, effective, and biocompatible strategy for controlled NO-mediated antibacterial applications.

Regev, a New Hybrid Fungicide for Control of Cercospora Leaf Spot on Sugar Beet

Cercospora leaf spot (CLS) is one of the most yield-limiting foliar disease of sugar beet in the United States. Standard practices to control this disease include selection of tolerant varieties, crop rotations, and reliance on fungicides. However, genetic resistance still requires some fungicides for acceptable control under high disease pressure, and there are only a limited number of fungicides registered for control of this disease. Regev® is a newly registered hybrid fungicide for sugar beet disease control that contains eight biological active ingredients from tea tree oil (TTO) and one active ingredient from the synthetic fungicide, difenoconazole. Tea tree oil provides a new and unique mode of activity against both fungal and bacterial plant pathogens, and it has a low resistance risk. Eight trials were conducted to evaluate Regev for efficacy against Cercospora leafspot, and sugar beet yield and quality benefits in Minnesota and Michigan. Five of the trials had slightly different treatments with the primary goal of allowing trialists to conduct trials with treatments that were appropriate for their locations. However, one of the trials at the Northwest Research and Outreach Center (NWROC) of the University of Minnesota in Crookston, Minnesota, was conducted three times over the years 2021, 2022, and 2023. Across the eight trials, spray programs that included Regev provided control of Cercospora leaf spot equal to standard fungicide programs.

Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates

Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 μg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.

Discovery of N-benzyl-6-methylpicolinamide as a potential scaffold for bleaching herbicides.

In pesticide research, bleaching herbicides have always been a hot topic. Our previous research showed that N-(4-fluorobenzyl)-2-methoxybenzamide is an innovative lead compound for bleaching herbicides. A total of 40 derivatives of picolinamides were prepared and evaluated for their herbicidal activity by Petri dish tests and postemergence trials. The structure-activity relationship (SAR) revealed that introducing electron-withdrawing groups at the 3- or 4-positions of the benzyl significantly enhances herbicidal activity. Furthermore, ZI-04 induced similar symptoms such as bleaching effect in treated weeds and accumulation of biosynthetic precursors for carotenoids as observed with diflufenican. ZI-04 also exhibited significant cross-resistance to diflufenican and had a lower resistance risk than diflufenican. N-benzyl-6-methylpicolinamides were discovered as a novel scaffold for bleaching herbicides. The accumulation of phytoene, phytofluene and ζ-Carotene in radish cotyledons, and cross-resistance observed with diflufenican, showed that title compounds can interfere with carotenoid biosynthesis. © 2024 Society of Chemical Industry.

Resistance and fitness costs of the Helicoverpa armigera after selection with the tetraniliprole newly developed diamide insecticide

The cotton bollworm (Helicoverpa armigera) (Lepidoptera: Noctuidae) is a highly destructive insect pest that feeds on more than 200 plants including cotton. Diamide insecticides are typically preferred to combat H. armigera. However, many reports of resistance to diamide insecticides such as chlorantraniliprole have been reported. Tetraniliprole is a novel diamide insecticide, but little is known about its resistance risk in H. armigera. After ten generations of treating H. armigera with tetraniliprole, neither the G4946 nor I4775 mutations were detected and no resistance to tetraniliprole was observed. The realized heritability (h2) was 0.094 after ten generations of selection with tetraniliprole, suggesting a low risk of resistance in H. armigera. Additionally, we found that the LD50 of tetraniliprole (4.01 μg/g) was lower than the LD50 of chlorantraniliprole (5.79 μg/g) in the susceptible strain. Molecular docking analysis also found a difference between the ryanodine receptor (RyR) binding sites of tetraniliprole and chlorantraniliprole, the tetraniliprole free binding energy to RyR was −6.9 kcal/mol, which was smaller than for chlorantraniliprole (−6.4 kcal/mol). Our study reveals that there is a low resistance risk to tetraniliprole in H. armigera, thus suggesting that tetraniliprole can be used as a substitute for other insecticides for this pest control.

Multi-label classification and features investigation of antimicrobial peptides with various functional classes

The challenge of drug-resistant bacteria to global public health has led to increased attention on antimicrobial peptides (AMPs) as a targeted therapeutic alternative with a lower risk of resistance. However, high production costs and limitations in functional class prediction have hindered progress in this field. In this study, we used multi-label classifiers with binary relevance and algorithm adaptation techniques to predict different functions of AMPs across a wide range of pathogen categories, including bacteria, mammalian cells, fungi, viruses, and cancer cells. Our classifiers attained promising AUC scores varying from 0.8492 to 0.9126 on independent testing data. Forward feature selection identified sequence order and charge as critical, with specific amino acids (C and E) as discriminative. These findings provide valuable insights for the design of antimicrobial peptides (AMPs) with multiple functionalities, thus contributing to the broader effort to combat drug-resistant pathogens.

Exploiting natural products to discover multitarget inhibitors of insect chitinolytic enzymes

Multitarget insecticides are more likely to achieve comprehensive regulation of insects with a low risk of resistance. Insect chitinolytic enzymes, including GH18 chitinases and GH20 β-N-acetyl-d-hexosaminidase, are attractive targets for multitarget insecticide design by virtue of their similar substrate binding mode and catalytic mechanism. On the other hand, natural products with diverse skeletal structures are potential repositories of chitinolytic enzyme inhibitors. This minireview first presents the theoretical basis of developing multitargeted inhibitors against insect chitinolytic enzymes and then focuses on the progress in developing multitarget inhibitors derived from natural products. These may provide ideas for the exploitation of novel pesticide leads from natural products by targeting multiple targets.

Prominent use of lactic acid bacteria in soil-plant systems

Lactic acid bacteria (LAB) are ubiquitous, Gram-positive, probiotic, and facultative aerophilic microorganisms. They are commonly found in wide range of environments including food-rich environments, decaying plants, milk products, the human gut, vaginal flora, and on the skin of various living organisms. These multifaceted bacteria have multiple roles including promoting food safety; promoting plant growth; improving soil, animal, and human health. They are also an integral part of sustainable farming strategies with a low risk of resistance to chemical pesticides, making them an environmentally friendly and effective way of managing pests and diseases and improving plant production. While the traditional role of LAB in food processing and human health sectors has been widely studied and documented, there is increasing attention to their additional roles that empirical evidences and research have validated such as serving as biofertilizers, biocontrol, and biostimulant agents in plant production through the production of bacteriocins, organic acids, and other compounds. However, there is still a gap in unlocking the relationship between LAB, soil, and plant hosts. Through a review of the literature and metadata, this review aims to discuss the less-explored relevance of LAB in soil-plant systems and spotlight the prospects for increased acceptance as sustainable and safe soil and plant health enhancers. The first part concentrates on analyzing the existing metadata, while the discussion part essentially focus on literature review.

Identifying the Unmet Medical Needs of HIV-Positive Subjects in Korea: Results of a Nationwide Online Survey.

An online survey was conducted in Korea to identify the unmet medical needs of people living with human immunodeficiency virus (HIV) (PLWH). Participants (n = 105) were mostly male (93.3%), aged >40 years (75.2%), and treated for ≥6 years post-diagnosis (61.9%). Most PLWH (71.4%) were very satisfied/satisfied with their HIV management. Areas of concern were quality of life (QoL) and mental health. Characteristics of a long-term therapeutic agent were 'low risk of resistance', 'high long-term viral suppression efficacy', and 'high degree of safety'. Pre-consultation QoL and mental health screening would be beneficial for the long-term success of HIV management.

Liposomal amphotericin B-the present.

Most invasive fungal infections are opportunistic in nature but the epidemiology is constantly changing, with new risk groups being identified. Neutropenia is a classical risk factor for fungal infections, while critically ill patients in the ICU are now increasingly at risk of yeast and mould infections. Factors to be considered when choosing antifungal treatment include the emergence of rarer fungal pathogens, the risk of resistance to azoles and echinocandins and the possibility of drug-drug interactions. Liposomal amphotericin B has retained its place in the therapeutic armamentarium based on its clinical profile: a broad spectrum of antifungal activity with a low risk of resistance, predictable pharmacokinetics with a rapid accumulation at the infection site (including biofilms), a low potential for drug-drug interactions and a low risk of acute and chronic treatment-limiting toxicities versus other formulations of amphotericin B. It is a suitable choice for the first-line empirical or pre-emptive treatment of suspected fungal infections in neutropenic haematology patients and is an excellent alternative for patients with documented fungal disease who can no longer tolerate or continue their first-line azole or echinocandin therapy, both in the haematology setting and in the ICU. Moreover, it is the first-line drug of choice for the treatment of invasive mucormycosis. Finally, liposomal amphotericin B is one of the few antifungal agents approved for use in children of all ages over 1 month and is included in paediatric-specific guidelines for the management of fungal disease.

A Membrane Curvature Modulated Lipopeptide to Broadly Combat Multidrug-Resistant Bacterial Pneumonia with Low Resistance Risk.

The extensive spread of multidrug resistance to Gram-negative bacteria has become a huge threat to human health, where peptide-based antibacterial agents have emerged as a powerful star weapon. Here we report a lipopeptide (LP-20) constructed nanomicelle with a different antibacterial mechanism of membrane curvature modulation, which induced dynamic membrane fission resulting in acceleration and enhancement of antibacterial activity to clinically isolated ESKAPE strains, including multidrug-resistant (MDR) pathogens. The minimum inhibitory concentration was reduced to 2-10 μM, and the minimum duration for killing was shortened to less than an hour by LP-20. This is an improvement over antimicrobial peptides and traditional antibiotics, such as ciprofloxacin and tetracycline, significantly enhancing antibacterial activity for MDR, and we observed no acquisition of resistance for one month. This accelerated germicidal mechanism was attributed to multitargeting with lipopolysaccharides, phosphoethanolamine, phosphatidylglycerol, and cardiolipin, and the synergetic interactions induced a high curvature of the bacterial membrane, which facilitated simultaneously efficient damage to both inner and outer membrane. The LP-20 effectively prolonged the lifetime of myositis mice with Escherichia coli MDR and pneumonia mice with Klebsiella pneumoniae through a hepatic metabolism with ignorable toxicity. This study provides critical information for the fabrication of lipopeptide-based nano-antibiotics for the efficient control of intractable MDR caused by Gram-negative pathogens.

Anti-Microbial Peptides from Medicinal Plants as an Alternative against Multi Drug Resistance

From its discovery to today, antibiotics have revolutionized medicine, and various antibiotics have been studied, discovered and put to significant application and it continues to be helpful in controlling infections. Nonetheless over application of these antibiotics have given rise to Antibiotic Resistance (AR) and Multidrug Resistant pathogens (MDR) against the various antibiotic’s agents. Anti-microbial peptides are being explored as an alternative against the prevalent issue of MDR and AR. Anti-microbial peptides are the part of host’s first line of defense mechanism of innate immune response, are small peptides its molecular weight is 2-10kDa, it holds amphiphillic properties, and is usually positively charged at neutral pH value. The advantages posed by anti-microbial peptides are many like broad antimicrobial spectrum, rapid action, and lower risk of resistance, low toxicity and high selectivity. It poses many therapeutic like anti-cancerous, anti-inflammatory, anti-bacterial, anti-fungal, anti-viral, and immunomodulator properties as well. Plants are good source of antimicrobial peptides. A variety of applications can be achieved with plant derived antimicrobial peptides, including antibacterial, insecticide, and infection control, including the control of cellular infection by viruses. AMPs exist in different molecular forms like Cyclotides, cyclic cysteine knot, defensin, thionin, snakin- Like, hevein-like, knottin like peptides etc. It is expected that anti-microbial peptides will have a positive impact on medicine, food, industries as antifouling agents and agriculture. The major objective of this review articleis to explore and identify important antimicrobial peptides in medicinal plants like Ocimum sanctum and Santalum album.

Keystone Malaria Symposium 2022: a vibrant discussion of progress made and challenges ahead from drug discovery to treatment

Keystone Malaria Symposium 2022: a vibrant discussion of progress made and challenges ahead from drug discovery to treatment

Sensitivity and Resistance Risk Assessment of Fusarium graminearum from Wheat to Prothioconazole.

Fusarium head blight (FHB), caused mainly by Fusarium graminearum, is one of the most devastating diseases of wheat. Prothioconazole is a broad-spectrum demethylation inhibitor fungicide with excellent efficacy against FHB. In this study, 235 strains of F. graminearum collected from different regions of Henan Province of China in 2016, 2017, and 2018 were randomly selected. The sensitivity of F. graminearum to prothioconazole was determined by the mycelial growth inhibition method. The results showed that the half maximal effective concentration (EC50) values of F. graminearum to prothioconazole ranged from 0.4742 to 3.4403 μg/ml, and the average EC50 value was 1.7758 ± 0.6667 μg/ml. The sensitivity frequency distribution presented a consequent unimodal curve, and thus the average EC50 value can be established as the baseline sensitivity of F. graminearum to prothioconazole. Ten strains of prothioconazole-resistant mutants were obtained by fungicide taming, and the resistance factor of the mutants ranged from 5.71 to 12.32. The genetic stability assay showed that resistance can be inherited stably for 10 generations. All mutants displayed different degrees of defects in vegetative growth, conidia formation, and pathogenicity compared with the parental strain. These results indicated that F. graminearum has a low risk of resistance to prothioconazole. Cross-resistance assay showed that no cross-resistance was found between prothioconazole and carbendazim, tebuconazole, phenamacril, and pydiflumetofen. Among all mutants, sequence analysis showed that no mutation site was found in cyp51A and cyp51B. Real-time PCR assays showed that the expression levels of cyp51A and cyp51B of the mutants were significantly increased after prothioconazole treatment for 24 h. In summary, our study provided a theoretical basis for the resistance risk assessment of F. graminearum to prothioconazole and scientific application of prothioconazole in controlling FHB.

Rosmarinus officinalis Might be Exploited as a Natural Antifouling Agent: A Potentially Promising Strategy for Curbing Membrane Biofouling

Membrane biofouling is the coverage of membrane surfaces due to undesirable development of biofilms causing a decrease and subsequent loss of productivity in water treatment settings. Continuous use of synthetic chemicals against biofouling is inept as it leads to the emergence of multi-antibiotic resistance. Application of natural products such as plants can be apt in curbing biofouling while checking the resistance challenge. This study aimed to evaluate the potential of Rosmarinus officinalis in the control of membrane biofouling. Bacteria from biofouling environments were subjected to a biofilm confirmation test and identified at cultural, morphological, biochemical and molecular levels. Leaves of R.officinalis were extracted in solvents of varying polarity and activities. These extracts were evaluated against bacterial biofilm formation via minimum biofilm inhibitory concentration (MBIC), minimum biofilm eradication concentration (MBEC) and mesocosm bioassays. Biofilm formation was confirmed in 68% of the isolates identified as Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus. The methanol and ethyl acetate extracts of R.officinalis indicated the least MICs (0.313mg/L and 1.25mg/L) against Pseudomonas aeruginosa and Staphylococcus aureus, respectively. Both extracts recorded the highest MBIC (50.00%) against Pseudomonas aeruginosa. The peak MBEC (57.88%) was obtained from the methanol extract against Staphylococcus aureus and this same extract inhibited 56.23% density of bacterial biofilms on glass slides.The methanol and ethyl acetate crude extracts of R. officinalis appreciably reduced bacterial biofilms; hence, this plant can be exploited as a natural antifouling agent, with reduced toxicity and low risk of resistance.

THE MOLECULAR APPROACH OF NATURAL PRODUCTS AS PANCREATIC CANCER TREATMENT: A REVIEW

Pancreatic cancer is one of the most feared types of cancer because of the high number of deaths from this disease. High cases of death are reported due to the ineffectiveness of the early detection process of this type of cancer and the low effectiveness of treatment. This review reports a natural product that has the potential to be used as an anticancer of the pancreas. Natural products are the focus of researchers due to the low risk of resistance and side effects of these products. The mechanism of action of natural products is also explored to ensure the activity of natural products as anticancer, including molecular mechanisms of action, cell cycle inhibitory activity, and promoting apoptosis. Natural products are ingredients that are widespread around us, very easy to find, and have a lot of evidence of their effectiveness as anticancer. It is hoped that this review will become the basis for researchers to conduct further exploration of natural products as pancreatic anticancer.

1438. Prevalence and Risk Factors for Extended Spectrum Betalactamases Among Hospitalized Patients with Community Acquired Pyelonephritis in Colombia

BackgroundUrinary tract infections (UTI) are the most frequent bacterial infection in hospitalized patients. Extented spectrum betalactamases (ESBL) producing bacteria causing UTI have become more prevalent. Escherichia coli (E. coli) is the most frequent ESBL producing bacteria isolated in UTI. This drug resistant organisms are associated with poorer outcomes for patients. In low income countries, approaching to and treating ESBL E. coli, represent a major challenge for health care centers. MethodsA retrospective cohort of adult patients with community acquired pyelonephritis caused by Escherichia coli was identified in a tertiary hospital in Colombia. Susceptibility was performed with Vitek (BioMerieux, France); extended spectrum beta lactamase (ESBL) production was defined phenotypically. Inclusion criteria were adult patients hospitalized with a positive urine culture for E. coli. Demographic and clinical characteristics were searched in electronic records. Risk factors associated with ESBL production were identified by using a multivariate logistic regression analysis.ResultsDuring 7 years 817 patients with pyelonephritis caused by E. coli were identified. 79 (9.7%) of them were caused by ESBL producers. Women were 66% and 408 (74.8% of them) had menopause. Mean age was 64.2 years (standard deviation of 19.1). Of the cohort, 481 (561.1%) had at least some comorbidity and was frequent to find diabetes (18.5%), immunosuppression due to oncologic disease or medications (18.4%), urolithiasis or previous surgical procedures (17%). After logistic regression, risk factors identified to predict ESBL production, were: being a man (aOR 5.4, 2.1-18.2), a woman with menopause (aOR 2.9, 1.3 -9.9), and the Charlson score (aOR 0.83, 0.73 – 0.96). Previous antibiotic use was not related to ESBL infection. ConclusionIn this relatively large cohort of patients with pyelonephritis caused by E. coli, ESBL production risk factors were not clearly identified other than sex and menopause. Curiously, Charlson score predicted a lower risk of resistance. Other factors (food consumptions and others) might be driving the resistance in the community in E. coli. Disclosures Jorge Cortes, MD, Pfizer (Research Grant or Support)

The effectiveness of moxifloxacin in the treatment of community-acquired pneumonia

The article presents the results of domestic and international studies of the use of the fourth-generation fluoroquinolone moxifloxacin in the treatment of commu-nity-acquired pneumonia and pneumonia caused by SARS-CoV-2. Analysis of the clinical use of moxifloxacin in the treatment of complications of the respiratory tract infec-tions indicates its high efficiency and bioavailability, a low risk of resistance, which makes it possible to recommend it for widespread use in the work of a practicing doctor. Ge-neric drug Maxicin (Yuria-Pharm), available as a 20 mg/ml concentrate in a 20 ml vial, can significantly reduce the cost of treatment and optimize infusion therapy by choosing both volume and solvent.