An analysis of postharvest fungal pathogens reveals temporal-spatial and host-pathogen associations with fungicide resistance-related mutations

Fungicides are the primary tools to control a wide range of postharvest fungal pathogens. Fungicide resistance is a widespread problem that has reduced fungicide efficacy. Resistance to FRAC 1 chemistries are associated with mutations in amino acid position 198 in the β-tubulin gene. In the current study we conducted a meta-analysis of β-tubulin sequences to infer temporal, spatial, plant host and pathogen genus patterns of fungicide resistance in postharvest fungal pathogens. In total, data was acquired from 2647 specimens from 12 genera of fungal phytopathogens residing in 53 countries, on over 200 hosts collected between 1926-2020. The specimens containing a position 198 mutation were globally distributed in a variety of pathosystems. Analyses showed that there is an association between the mutation and the year an isolate was collected, the pathogen genus, the pathogen host and the collection region. Interestingly, fungicide resistant β-tubulin genotypes have been in a decline since their peak between 2005-2009. FRAC 1 fungicide usage data followed a similar pattern in that applications have been in a decline since their peak between 1997 and 2003. The data shows that, with the reduction of selection pressure, FRAC 1 fungicide resistance in fungal populations will decline within 5-10 years. Based on this line of evidence, we contend that a β-tubulin position 198 mutation has uncharacterized fitness cost(s) on fungi in nature. The compiled dataset can inform end users on the regions and hosts that are most prone to contain resistant pathogens and assist decisions concerning fungicide resistant management strategies.

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Point Mutations in the β-Tubulin of Phytophthora sojae Confer Resistance to Ethaboxam

Phytopathology ◽

10.1094/phyto-01-19-0032-r ◽

2019 ◽

Vol 109 (12) ◽

pp. 2096-2106 ◽

Cited By ~ 3

Author(s):

Qin Peng ◽

Zhiwen Wang ◽

Yuan Fang ◽

Weizhen Wang ◽

Xingkai Cheng ◽

...

Keyword(s):

Fungicide Resistance ◽

Germination Rate ◽

Management Strategies ◽

Resistance Management ◽

Point Mutations ◽

Phytophthora Sojae ◽

Cross Resistance ◽

Baseline Sensitivity ◽

Resistant Mutants ◽

Β Tubulin

Ethaboxam is a β-tubulin inhibitor registered for the control of oomycete pathogens. The current study was established to determine the ethaboxam sensitivity of the plant pathogen Phytophthora sojae and investigate the potential for the emergence of fungicide resistance. The effective concentration for 50% inhibition (EC50) of 112 Phytophthora sojae isolates exhibited a unimodal distribution with a mean EC50 for ethaboxam of 0.033 µg/ml. Establishing this baseline sensitivity provided critical data for monitoring changes in ethaboxam-sensitivity in field populations. The potential for fungicide resistance was investigated using adaptation on ethaboxam-amended V8 agar, which resulted in the isolation of 20 resistant mutants. An assessment of the biological characteristics of the mutants including mycelial growth, sporulation, germination rate and pathogenicity indicated that the resistance risk in Phytophthora sojae was low to medium with no cross-resistance between ethaboxam and cymoxanil, metalaxyl, flumorph, and oxathiapiprolin being detected. However, positive cross-resistance was found between ethaboxam and zoxamide for Q8L and I258V but negative cross-resistance for C165Y. Further investigation revealed that the ethaboxam-resistant mutants had point mutations at amino acids Q8L, C165Y, or I258V of their β-tubulin protein sequences. CRISPR/Cas9-mediated transformation experiments confirmed that the Q8L, C165Y, or I258V mutations could confer ethaboxam resistance in Phytophthora sojae and that the C165Y mutation induces high levels of resistance. Taken together, the results of the study provide essential data for monitoring the emergence of resistance and resistance management strategies for ethaboxam, as well as for improving the design of novel β-tubulin inhibitors for future development.

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At Least Two Origins of Fungicide Resistance in Grapevine Downy Mildew Populations

Applied and Environmental Microbiology ◽

10.1128/aem.00507-07 ◽

2007 ◽

Vol 73 (16) ◽

pp. 5162-5172 ◽

Cited By ~ 96

Author(s):

Wei-Jen Chen ◽

François Delmotte ◽

Sylvie Richard Cervera ◽

Lisette Douence ◽

Charles Greif ◽

...

Keyword(s):

Plant Pathogen ◽

Fungicide Resistance ◽

Fungal Pathogens ◽

Plant Pathogens ◽

Plasmopara Viticola ◽

Isolated Populations ◽

Grapevine Downy Mildew ◽

First Case ◽

Wide Range ◽

Pathogen Populations

ABSTRACT Quinone outside inhibiting (QoI) fungicides represent one of the most widely used groups of fungicides used to control agriculturally important fungal pathogens. They inhibit the cytochrome bc 1 complex of mitochondrial respiration. Soon after their introduction onto the market in 1996, QoI fungicide-resistant isolates were detected in field plant pathogen populations of a large range of species. However, there is still little understanding of the processes driving the development of QoI fungicide resistance in plant pathogens. In particular, it is unknown whether fungicide resistance occurs independently in isolated populations or if it appears once and then spreads globally by migration. Here, we provide the first case study of the evolutionary processes that lead to the emergence of QoI fungicide resistance in the plant pathogen Plasmopara viticola. Sequence analysis of the complete cytochrome b gene showed that all resistant isolates carried a mutation resulting in the replacement of glycine by alanine at codon 143 (G143A). Phylogenetic analysis of a large mitochondrial DNA fragment including the cytochrome b gene (2,281 bp) across a wide range of European P. viticola isolates allowed the detection of four major haplotypes belonging to two distinct clades, each of which contains a different QoI fungicide resistance allele. This is the first demonstration that a selected substitution conferring resistance to a fungicide has occurred several times in a plant-pathogen system. Finally, a high population structure was found when the frequency of QoI fungicide resistance haplotypes was assessed in 17 French vineyards, indicating that pathogen populations might be under strong directional selection for local adaptation to fungicide pressure.

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Determination of Natural Resistance Frequencies in Penicillium digitatum Using a New Air-Sampling Method and Characterization of Fludioxonil- and Pyrimethanil-Resistant Isolates

Phytopathology ◽

10.1094/phyto-100-8-0738 ◽

2010 ◽

Vol 100 (8) ◽

pp. 738-746 ◽

Cited By ~ 19

Author(s):

L. Kanetis ◽

H. Förster ◽

J. E. Adaskaveg

Keyword(s):

Concentration Gradient ◽

Fungicide Resistance ◽

Sampling Method ◽

Management Strategies ◽

Air Sampling ◽

Penicillium Digitatum ◽

Natural Resistance ◽

Fungicide Sensitivity ◽

Laboratory Selection ◽

Wide Range

Fungicide resistance was identified in natural populations of Penicillium digitatum, the causal agent of green mold of citrus, to two of three new postharvest fungicides before their commercial use. Using a new air-sampling method where large populations of the pathogen in citrus packinghouses were exposed to agar plates with a continuous, wide-range fungicide concentration gradient, isolates with reduced sensitivity to fludioxonil or pyrimethanil were obtained. Resistance frequencies to fludioxonil and pyrimethanil were calculated as 9.5 × 10–7 to 1.5 × 10–5 and 7.3 × 10–6 to 6.2 × 10–5, respectively. No isolates resistant to azoxystrobin were detected. Isolates with reduced sensitivity to fludioxonil or pyrimethanil were also obtained in laboratory selection studies, where high concentrations of conidial mixtures of isolates sensitive to the three fungicides were plated onto agar amended with each fungicide at 10 μg/ml. Isolates obtained from fludioxonil selection plates in laboratory and packinghouse experiments were placed into two categories based on mycelial growth: moderately resistant isolates had 50% effective concentration (EC50) values of 0.1 to 0.82 μg/ml and highly resistant isolates had EC50 values > 1.5 μg/ml. Isolates resistant to pyrimethanil all had EC50 values >8 μg/ml. Representative isolates of the two categories with reduced sensitivity to fludioxonil varied widely in their virulence and sporulation capacity as measured by the incidence of decay and degree of sporulation on inoculated fruit, respectively, whereas pyrimethanil-resistant isolates were mostly similar to the wild-type isolate. Fungicide sensitivity characteristics for isolates from fludioxonil and pyrimethanil selection plates remained stable after passages on nonamended agar, and disease could not be controlled after treatment with the respective fungicides. Types of fungicide resistance were visualized on thiabendazole- (TBZ) and imazalil-amended selection plates that were exposed in packinghouses where resistance to these fungicides was known to occur. The qualitative, single-site resistance to the benzimidazole TBZ was visualized by two distinct subpopulations in regard to fungicide sensitivity, whereas the quantitative, multi-site resistance to the demethylation inhibitor imazalil was apparent as a continuous density gradient of colonies along the fungicide concentration gradient. Types of resistance could not be assigned to fludioxonil or pyrimethanil because a limited number of resistant colonies was obtained on each plate. Thus, with this new method, we were able to estimate fungicide resistance frequencies as well as characterize and visualize types of resistance within populations of a fungal species. This information will be used to design resistance management strategies for previous and newly registered postharvest fungicides of citrus.

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Anti-fungal secondary metabolites and hydrolytic enzymes from rhizospheric bacteria in crop protection: a review

Journal of Bangladesh Academy of Sciences ◽

10.3329/jbas.v44i2.51452 ◽

2021 ◽

Vol 44 (2) ◽

pp. 69-84

Author(s):

Farhana Tasnim Chowdhury ◽

Nazia Rifat Zaman ◽

Mohammad Riazul Islam ◽

Haseena Khan

Keyword(s):

Secondary Metabolites ◽

Plant Growth ◽

Fungal Pathogens ◽

Hydrolytic Enzymes ◽

Plant Growth Promoting Rhizobacteria ◽

Field Conditions ◽

Plant Host ◽

Wide Range ◽

Plant Growth Promoting ◽

Growth Promoting

Plant growth promoting rhizobacteria (PGPR) residing in soil rhizosphere provide enormous beneficial effects to a plant host producing diverse secondary metabolites and enzymes useful for plant growth and protection. Siderophores, antibiotics, volatile compounds and hydrolytic enzymes are the major molecules secreted by the PGPRs, which have substantial antifungal properties and can provide plant protection. These compounds are responsible for the lysis and hyperparasitism of antagonists against deleterious fungal pathogens. Siderophore-producing PGPRs function by depriving the pathogen of iron nutrition. Antibiotics have been reported to be involved in the suppression of different fungal pathogens by inducing fungistasis, inhibition of spore germination, lysis of fungal mycelia. The PGPRs also secrete a wide range of low molecular weight volatile organic compounds (VOCs) that inhibit mycelial growth, sporulation, germination of phytophathogenic fungi, etc. Hydrolytic enzymes, mostly chitinase, protease and cellulose, lyse the cell wall of fungi. Therefore, plant growth-promoting rhizobacteria can be considered as an effective, eco-friendly, and sustainable replacement to the chemical fungicides. There are many PGPRs that perform very well in controlled conditions but not in field conditions, and hence the commercializing of hese products is not easy. Development of formulations with increased shelf life, a broad spectrum of action and consistent performance under field conditions can pave the way for commercializing the PGPRs at a faster rate. Journal of Bangladesh Academy of Sciences, Vol. 44, No. 2, 69-84, 2020

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Understanding Limited Use of Amplification in Infants and Children Who Are Hard of Hearing

Perspectives on Hearing and Hearing Disorders in Childhood ◽

10.1044/hhdc25.1.15 ◽

2015 ◽

Vol 25 (1) ◽

pp. 15-23 ◽

Cited By ~ 1

Author(s):

Ryan W. McCreery ◽

Elizabeth A. Walker ◽

Meredith Spratford

Keyword(s):

Hard Of Hearing ◽

Hearing Aid ◽

Management Strategies ◽

Infants And Children ◽

Future Research ◽

Research Needs ◽

Case Examples ◽

Hearing Aid Use ◽

Wide Range ◽

In Infants And Children

The effectiveness of amplification for infants and children can be mediated by how much the child uses the device. Existing research suggests that establishing hearing aid use can be challenging. A wide range of factors can influence hearing aid use in children, including the child's age, degree of hearing loss, and socioeconomic status. Audiological interventions, including using validated prescriptive approaches and verification, performing on-going training and orientation, and communicating with caregivers about hearing aid use can also increase hearing aid use by infants and children. Case examples are used to highlight the factors that influence hearing aid use. Potential management strategies and future research needs are also discussed.

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Time in range for multiple technologies in type 1 diabetes: a systematic review and network meta-analysis

10.2337/figshare.12116691 ◽

2020 ◽

Author(s):

Anthony Pease ◽

Clement Lo ◽

Arul Earnest ◽

Velislava Kiriakova ◽

Danny Liew ◽

...

Keyword(s):

Systematic Review ◽

Type 1 Diabetes ◽

Closed Loop ◽

Meta Analysis ◽

Management Strategies ◽

Glucose Testing ◽

Closed Loop Systems ◽

Percent Time ◽

Time In Range

Background: Time-in-range is a key glycaemic metric, and comparisons of management technologies for this outcome are critical to guide device selection. Purpose: We conducted a systematic review and network meta-analysis to compare and rank technologies for time in glycaemic ranges. Data sources: We searched All Evidenced Based Medicine Reviews, CINAHL, EMBASE, MEDLINE, MEDLINE In-Process and other non-indexed citations, PROSPERO, PsycINFO, PubMed, and Web of Science until 24 April, 2019. Study selection: We included randomised controlled trials >2 weeks duration comparing technologies for management of type 1 diabetes in adults (>18 years of age), excluding pregnant women. Data extraction: Data were extracted using a predefined template. Outcomes were percent time with sensor glucose levels 3.9–10.0mmol/l (70–180mg/dL), >10.0mmol/L (180mg/dL), and <3.9mmol/L (70mg/dL). Data synthesis: We identified 16,772 publications, of which 14 eligible studies compared eight technologies comprising 1,043 participants. Closed loop systems lead to greater percent time-in-range than any other management strategy and was 17.85 (95% predictive interval [PrI] 7.56–28.14) higher than usual care of multiple daily injections with capillary glucose testing. Closed loop systems ranked best for percent time-in-range or above range utilising surface under the cumulative ranking curve (SUCRA–98.5 and 93.5 respectively). Closed loop systems also ranked highly for time below range (SUCRA–62.2). Limitations: Overall risk of bias ratings were moderate for all outcomes. Certainty of evidence was very low. Conclusions: In the first integrated comparison of multiple management strategies considering time-in-range, we found that the efficacy of closed loop systems appeared better than all other approaches.

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Control of Winged Waterprimrose (Jussiaea decurrens) and Northern Jointvetch (Aeschynomene virginica) with Fungal Pathogens

Weed Science ◽

10.1017/s0043174500044477 ◽

1979 ◽

Vol 27 (5) ◽

pp. 497-501 ◽

Cited By ~ 46

Author(s):

C. D. Boyette ◽

G. E. Templeton ◽

R. J. Smith

Keyword(s):

Oryza Sativa ◽

Glycine Max ◽

Fungal Pathogens ◽

Liquid Culture ◽

Field Experiments ◽

Colletotrichum Gloeosporioides ◽

Pathogenic Fungus ◽

Field Tests ◽

Wide Range ◽

Growing Region

An indigenous, host-specific, pathogenic fungus that parasitizes winged waterprimrose [Jussiaea decurrens(Walt.) DC.] is endemic in the rice growing region of Arkansas. The fungus was isolated and identified asColletotrichum gloeosporioides(Penz.) Sacc. f.sp. jussiaeae(CGJ). It is highly specific for parasitism of winged waterprimrose and not parasitic on creeping waterprimrose (J. repensL. var.glabrescensKtze.), rice (Oryza sativaL.), soybeans [Glycine max(L.) Merr.], cotton (Gossypium hirsutumL.), or 4 other crops and 13 other weeds. The fungus was physiologically distinct from C.gloeosporioides(Penz.) Sacc. f. sp.aeschynomene(CGA), an endemic anthracnose pathogen of northern jointvetch[Aeschynomene virginica(L.) B.S.P.], as indicated by cross inoculations of both weeds. Culture in the laboratory and inoculation of winged waterprimrose in greenhouse, growth chamber and field experiments indicated that the pathogen was stable, specific, and virulent in a wide range of environments. The pathogen yielded large quantities of spores in liquid culture. It is suitable for control of winged waterprimrose. Winged waterprimrose and northern jointvetch were controlled in greenhouse and field tests by application of spore mixtures of CGJ and CGA at concentrations of 1 to 2 million spores/ml of each fungus in 94 L/ha of water; the fungi did not damage rice or nontarget crops.

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Trends in Molecular Diagnosis and Diversity Studies for Phytosanitary Regulated Xanthomonas

Microorganisms ◽

10.3390/microorganisms9040862 ◽

2021 ◽

Vol 9 (4) ◽

pp. 862

Author(s):

Vittoria Catara ◽

Jaime Cubero ◽

Joël F. Pothier ◽

Eran Bosis ◽

Claude Bragard ◽

...

Keyword(s):

Molecular Diagnosis ◽

Bacterial Species ◽

Management Strategies ◽

Diagnostic Methods ◽

Plant Diseases ◽

Wild Plants ◽

Future Climate Change ◽

Climate Change Scenarios ◽

Wide Range ◽

Diversity Studies

Bacteria in the genus Xanthomonas infect a wide range of crops and wild plants, with most species responsible for plant diseases that have a global economic and environmental impact on the seed, plant, and food trade. Infections by Xanthomonas spp. cause a wide variety of non-specific symptoms, making their identification difficult. The coexistence of phylogenetically close strains, but drastically different in their phenotype, poses an added challenge to diagnosis. Data on future climate change scenarios predict an increase in the severity of epidemics and a geographical expansion of pathogens, increasing pressure on plant health services. In this context, the effectiveness of integrated disease management strategies strongly depends on the availability of rapid, sensitive, and specific diagnostic methods. The accumulation of genomic information in recent years has facilitated the identification of new DNA markers, a cornerstone for the development of more sensitive and specific methods. Nevertheless, the challenges that the taxonomic complexity of this genus represents in terms of diagnosis together with the fact that within the same bacterial species, groups of strains may interact with distinct host species demonstrate that there is still a long way to go. In this review, we describe and discuss the current molecular-based methods for the diagnosis and detection of regulated Xanthomonas, taxonomic and diversity studies in Xanthomonas and genomic approaches for molecular diagnosis.

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More than 50 long-term effects of COVID-19: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-021-95565-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sandra Lopez-Leon ◽

Talia Wegman-Ostrosky ◽

Carol Perelman ◽

Rosalinda Sepulveda ◽

Paulina A. Rebolledo ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Management Strategies ◽

Original Data ◽

Long Term Effects ◽

Pooled Prevalence ◽

Attention Disorder ◽

Initial Recovery ◽

Meta Analyses

AbstractCOVID-19 can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery. This systematic review and meta-analysis aims to identify studies assessing the long-term effects of COVID-19. LitCOVID and Embase were searched to identify articles with original data published before the 1st of January 2021, with a minimum of 100 patients. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. PRISMA guidelines were followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included (age 17–87 years). The included studies defined long-COVID as ranging from 14 to 110 days post-viral infection. It was estimated that 80% of the infected patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). Multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

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Association between CYP3A5 Polymorphism and Statin-Induced Adverse Events: A Systemic Review and Meta-Analysis

Journal of Personalized Medicine ◽

10.3390/jpm11070677 ◽

2021 ◽

Vol 11 (7) ◽

pp. 677

Author(s):

Jeong Yee ◽

Hamin Kim ◽

Yunhee Heo ◽

Ha-Young Yoon ◽

Gonjin Song ◽

...

Keyword(s):

Adverse Events ◽

Web Of Science ◽

Meta Analysis ◽

Statistical Significance ◽

Systemic Review ◽

Event Risk ◽

Total Data ◽

Lipophilic Statin ◽

The Relationship ◽

Review Manager

Purpose: Cytochrome P450 (CYP) is involved in the metabolism of statins; CYP3A5 is the main enzyme responsible for lipophilic statin metabolism. However, the evidence of the association between CYP3A5*3 polymorphism and the risk of statin-induced adverse events remains unclear. Therefore, this study aimed to perform a systematic review and meta-analysis to investigate the relationship between the CYP3A5*3 polymorphism and the risk of statin-induced adverse events. Methods: The PubMed, Web of Science, and EMBASE databases were searched for qualified studies published until August 2020. Observational studies that included the association between statin-induced adverse events and the CYP3A5*3 polymorphism were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated to assess the strength of the relationship. The Mantel–Haenszel method was used to provide the pooled ORs. Heterogeneity was estimated with I2 statistics and publication bias was determined by Begg’s and Egger’s test of the funnel plot. Data analysis was performed using Review Manager (version 5.4) and R Studio (version 3.6). Results: In total, data from 8 studies involving 1614 patients were included in this meta-analysis. The CYP3A5*3 polymorphism was found to be associated with the risk of statin-induced adverse events (*3/*3 vs. *1/*1 + *1/*3: OR = 1.40, 95% CI = 1.08–1.82). For myopathy, the pooled OR was 1.30 (95% CI: 0.96–1.75). The subgroup analysis of statin-induced myopathy revealed a trend, which did not achieve statistical significance. Conclusions: This meta-analysis demonstrated that the CYP3A5*3 polymorphism affected statin-induced adverse event risk. Therefore, CYP3A5 genotyping may be useful to predict statin toxicity.

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