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1.
Medicine (Baltimore) ; 99(11): e19494, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176090

RESUMO

As detection rates of non-albicans Candida species are increasing, determining their pathogen profiles and antifungal susceptibilities is important for antifungal treatment selection. We identified the antifungal susceptibility patterns and predictive factors for mortality in candidemia.A multicenter retrospective analysis of patients with at least 1 blood culture positive for Candida species was conducted. Candida species were classified into 3 groups (group A, Candia albicans; group B, Candida tropicalis, and Candida parasilosis; group C, Candida glabrata and Candida krusei ) to analyze the susceptibility patterns, first-line antifungal administered, and mortality. Univariate and multivariate comparisons between outcomes were performed to identify mortality risk factors.In total, 317 patients were identified, and 136 (42.9%) had recorded mortality. Echinocandin susceptibility was higher for group A than group B (111/111 [100%] vs 77/94 [81.9%], P < .001). Moreover, group A demonstrated higher fluconazole susceptibility (144/149 [96.6%] vs 39/55 [70.9%], P < .001) and lower mortality (68 [45.3%] vs 34 [61.8%], P = .036) than those of group C. In the multivariate analysis, the sequential organ failure assessment score (odds ratio OR 1.351, 95% confidence interval 1.067-1.711, p = 0.013) and positive blood culture on day 7 of hospitalization (odds ratio 5.506, 95% confidence interval, 1.697-17.860, P = .004) were associated with a higher risk of mortality.Patients with higher sequential organ failure assessment scores and sustained positive blood cultures have an increased risk of mortality.


Assuntos
Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidemia/tratamento farmacológico , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Idoso , Antifúngicos/farmacologia , Candidemia/mortalidade , Feminino , Fluconazol/farmacologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Valor Preditivo dos Testes , República da Coreia , Estudos Retrospectivos , Fatores de Risco
2.
Rev Soc Bras Med Trop ; 53: e20190214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049200

RESUMO

INTRODUCTION: The aim of this study was to evaluate some virulence factors in Candida albicans isolates from patients with onychomycosis and determine the correlation between these factors and the antifungal resistance profile. METHODS: Seventy species of C. albicans were confirmed using polymerase chain reaction amplification of the HWP1 gene. According to the Clinical & Laboratory Standards Institute guidelines, the susceptibility profile of four antifungal agents was investigated, and the production of aspartyl protease, phospholipase, haemolysin, and biofilm was determined. The correlation between these profiles was also investigated. RESULTS: The isolates indicated different levels of resistance and production of virulence factors. Significant correlations were observed between the minimum inhibitory concentration (MIC) of fluconazole/itraconazole and biofilm production, between phospholipase production and fluconazole/itraconazole MIC, and between fluconazole MIC and hemolytic activity in C. albicans isolates. The results also showed significant correlations between phospholipase activity and biofilm production. CONCLUSIONS: Our findings will contribute to a better understanding of the pathogenesis of C. albicans and characterize the relationship between virulence factors and antifungal resistance, which may suggest new therapeutic strategies considering the possible involvement of the virulence mechanism in the effectiveness of treatment.


Assuntos
Antifúngicos/farmacologia , Candida albicans/patogenicidade , Unhas/microbiologia , Onicomicose/microbiologia , Fatores de Virulência , Ácido Aspártico Proteases/biossíntese , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/ultraestrutura , Farmacorresistência Fúngica , Hemólise , Humanos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Fosfolipases/biossíntese , Reação em Cadeia da Polimerase
3.
World J Microbiol Biotechnol ; 36(2): 28, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002680

RESUMO

In Saccharomyces cerevisiae, los1 encodes a nuclear tRNA exporter. Despite the non-essentiality, the deletion of los1 has been shown to extend replicative life span in yeast. Here, we characterized AfuXpot, the los1 homologue in human pathogen Aspergillus fumigatus and found that it is continuously expressed during fungal growth. Microscopic examination of an AfuXpot-GFP-expressing transformant confirmed the nuclear localization of the fusion protein. The targeted gene deletion affirmed the non-essential role of AfuXpot in hyphal growth and sporulation. However, the growth of the deletion mutant was affected by amino acid, but not glucose, deprivation. The susceptibility of the deletant strain to protein and DNA/RNA synthesis inhibitors was also altered. Using bioinformatics tools, some transcription factor binding sites were predicted in AfuXpot promoter. Expression analyses of potential AfuXpot-interacting genes showed a marked down-regulation of sfp1 and mtr10 homologues in ΔAfuXpot strain. Our data demonstrates some conserved aspects of AfuXpot as a tRNA exporter in A. fumigatus.


Assuntos
Aminoácidos/metabolismo , Aspergillus fumigatus/crescimento & desenvolvimento , Aspergillus fumigatus/genética , Proteínas Fúngicas/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , RNA Fúngico/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Aminoácidos/deficiência , Aspergillus fumigatus/metabolismo , Clonagem Molecular , DNA Fúngico/genética , DNA Fúngico/isolamento & purificação , Farmacorresistência Fúngica , Proteínas Fúngicas/genética , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Glucose/metabolismo , Hifas/crescimento & desenvolvimento , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Regiões Promotoras Genéticas , RNA Fúngico/isolamento & purificação , RNA de Transferência/genética , RNA de Transferência/isolamento & purificação , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
4.
Phytopathology ; 110(3): 694-702, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32017671

RESUMO

Botrytis cinerea, the causal agent of gray mold, has high genetic diversity and a broad host range. In Vitis sp. and Prunus spp., B. cinerea causes pre- and postharvest diseases, and fungicides are routinely applied to prevent yield loss. In total, 535 isolates of B. cinerea collected from Vitis sp. and Prunus spp. in 2012, 2016, and 2017 were genotyped using 18 microsatellite markers and the transposable elements (TEs) Boty and Flipper. Only nine of the polymorphic markers and the two TEs were considered informative and retained for the final analyses. Of the 532 isolates, 297 were tested for resistance to seven fungicides representing six Fungicide Resistance Action Committee classes. After clone correction, 295 multilocus genotype groups were retained across the 3 years in 326 individuals, and four genetic subpopulations were detected. High levels of clonality were observed across the dataset. Significant pairwise differentiation was detected among years, locations, and TE composition. However, most of the diversity observed was within a subpopulation and not among subpopulations. No genetic differentiation was detected among resistant and sensitive isolates for individual fungicide classes. When resistance to the total number of fungicides was compared, regardless of the fungicide class, significant differentiation was detected among isolates that are resistant to two fungicide classes and those resistant to three or four fungicide groups. Fungicide resistance frequencies were stable for most chemistries evaluated with the exception of fluopyram, which increased from 2012 to 2016/2017.


Assuntos
Fungicidas Industriais , Prunus , Vitis , Botrytis , California , Farmacorresistência Fúngica , Genética Populacional , Doenças das Plantas
5.
MMWR Morb Mortal Wkly Rep ; 69(1): 6-9, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31917780

RESUMO

Candida auris is a globally emerging yeast that causes outbreaks in health care settings and is often resistant to one or more classes of antifungal medications (1). Cases of C. auris with resistance to all three classes of commonly prescribed antifungal drugs (pan-resistance) have been reported in multiple countries (1). C. auris has been identified in the United States since 2016; the largest number (427 of 911 [47%]) of confirmed clinical cases reported as of October 31, 2019, have been reported in New York, where C. auris was first detected in July 2016 (1,2). As of June 28, 2019, a total of 801 patients with C. auris were identified in New York, based on clinical cultures or swabs of skin or nares obtained to detect asymptomatic colonization (3). Among these patients, three were found to have pan-resistant C. auris that developed after receipt of antifungal medications, including echinocandins, a class of drugs that targets the fungal cell wall. All three patients had multiple comorbidities and no known recent domestic or foreign travel. Although extensive investigations failed to document transmission of pan-resistant isolates from the three patients to other patients or the environment, the emergence of pan-resistance is concerning. The occurrence of these cases underscores the public health importance of surveillance for C. auris, the need for prudent antifungal prescribing, and the importance of conducting susceptibility testing on all clinical isolates, including serial isolates from individual patients, especially those treated with echinocandin medications. This report summarizes investigations related to the three New York patients with pan-resistant infections and the subsequent actions conducted by the New York State Department of Health and hospital and long-term care facility partners.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Farmacorresistência Fúngica , Idoso , Antifúngicos/classificação , Candida/isolamento & purificação , Humanos , Pessoa de Meia-Idade , New York
6.
BMC Infect Dis ; 20(1): 55, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952505

RESUMO

BACKGROUND: Candidaemia is the most common form of invasive candidiasis. Resistant Candida blood stream infection (BSI) is rising, with limitations on the development of broader-spectrum antifungal agents worldwide. Our study aimed to identify the occurrence of antifungal-resistant candidaemia and the distribution of these species, determine the risk factors associated with antifungal resistance and evaluate the association of antifungal-resistant candidaemia with the length of intensive care unit (ICU) and hospital stay and with 30-day mortality. METHODS: A retrospective cohort study was conducted at King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia. Adult patients diagnosed with candidaemia from January 2006 to December 2017 were included. RESULTS: A total of 196 BSIs were identified in 94 males (49.74%) and 95 females (50.26%). C. glabrata was the most commonly isolated Candida species, with 59 (30%), followed by C. albicans with 46 (23%). Susceptibility data were available for 122/189 patients, of whom 26/122 (21%) were resistant to one or more antifungals. C. parapsilosis with available sensitivity data were found in 30/122 isolates, of which 10/30 (33%) were resistant to fluconazole. Risk factors significantly associated with antifungal-resistant candidaemia included previous echinocandin exposure (odds ratio (OR) =1.38; 95% confidence interval (CI) (1.02-1.85); P = 0.006) and invasive ventilation (OR = 1.3; 95% CI (1.08-1.57); P = 0.005). The median length of ICU stay was 29 days [range 12-49 days] in the antifungal-resistant group and 18 days [range 6.7-37.5 days] in the antifungal-sensitive group (P = 0.28). The median length of hospital stay was 51 days [range 21-138 days] in the antifungal-resistant group and 35 days [range 17-77 days] in the antifungal-sensitive group (P = 0.09). Thirty-day mortality was 15 (57.7%) and 54 (56.25%) among the antifungal-resistant and antifungal-sensitive groups, respectively (OR = 1.01; 95% CI (0.84-1.21); P = 0.89). CONCLUSIONS: Our results indicate a high frequancy of non- C. albicans candidaemia. The rise in C. parapsilosis resistance to fluconazole is alarming. Further studies are required to confirm this finding.


Assuntos
Candidemia/diagnóstico , Farmacorresistência Fúngica , Adulto , Idoso , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candida glabrata/efeitos dos fármacos , Candida glabrata/isolamento & purificação , Candidemia/tratamento farmacológico , Candidemia/microbiologia , Feminino , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Arábia Saudita
7.
Plant Dis ; 104(3): 893-903, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31891552

RESUMO

Target spot of tomato caused by Corynespora cassiicola is one of the most economically destructive diseases of tomato in Florida. A collection of 123 isolates from eight counties in Florida were evaluated for sensitivity to azoxystrobin and fenamidone based on mycelial growth inhibition (MGI), spore germination (SG), detached leaflet assays (DLAs), and sequence-based analysis of the cytochrome b gene (cytb). Cleavage of cytb by restriction enzyme (Fnu4HI) revealed the presence of a mutation conferring a glycine (G) to alanine (A) mutation at amino acid position 143 (G143A) in approximately 90% of the population, correlating with quinone outside inhibitor (QoI) resistance based on MGI (<40% at 5 µg/ml), SG (<50% at 1 and 10 µg/ml), and DLA (<10% severity reduction). The mutation conferring a phenylalanine (F) to leucine (L) substitution at position 129 (F129L) was confirmed in moderately resistant isolates (#9, #19, and #74) based on MGI (40 to 50% at 5 µg/ml), SG (<50% at 1 µg/ml and >50% at 10 µg/ml), and DLA (>10% and <43% severity reduction) for both QoI fungicides, whereas sensitive isolates (#1, #4, #7, #28, #29, #46, #61, #74, #75, #76, #91, #95, and #118) based on MGI (>50% at 5 µg/ml), SG (>50% at 1 µg/ml and 10 µg/ml), and DLA (>50% severity reduction) correlated to non-mutation-containing isolates or those with a silent mutation. This study indicates that QoI resistance among C. cassiicola isolates from tomato is widespread in Florida and validates rapid screening methods using MGI or molecular assays to identify resistant isolates in future studies.


Assuntos
Fungicidas Industriais , Lycopersicon esculentum , Farmacorresistência Fúngica , Florida , Proteínas Fúngicas , Doenças das Plantas
8.
BMC Infect Dis ; 20(1): 13, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906888

RESUMO

BACKGROUND: The development of respiratory infections secondary to Aspergillus spp. spores found ubiquitously in the ambient environment is uncommon in immunocompetent patients. Previous reports of invasive upper airway aspergillosis in immunocompetent patients have generally demonstrated the efficacy of treatment regimens utilizing antifungal agents in combination with periodic endoscopic debridement, with symptoms typically resolving within months of initiating therapy. CASE PRESENTATION: A 43-year-old previously healthy female presented with worsening respiratory symptoms after failing to respond to long-term antibiotic treatment of bacterial sinusitis. Biopsy of her nasopharynx and trachea revealed extensive fungal infiltration and Aspergillus fumigatus was isolated on tissue culture. Several months of oral voriconazole monotherapy failed to resolve her symptoms and she underwent mechanical debridement for symptom control. Following transient improvement, her symptoms subsequently returned and failed to fully resolve in spite of increased voriconazole dosing and multiple additional tissue debridements over the course of many years. CONCLUSIONS: Invasive upper airway aspergillosis is exceedingly uncommon in immunocompetent patients. In the rare instances that such infections do occur, combinatorial voriconazole and endoscopic debridement is typically an efficacious treatment approach. However, some patients may continue to experience refractory symptoms. In such cases, continued aggressive treatment may potentially slow disease progression even if complete disease resolution cannot be achieved.


Assuntos
Antifúngicos/uso terapêutico , Desbridamento , Aspergilose Pulmonar Invasiva/terapia , Adulto , Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/isolamento & purificação , Terapia Combinada , Farmacorresistência Fúngica , Endoscopia , Feminino , Humanos , Aspergilose Pulmonar Invasiva/microbiologia , Nasofaringe/microbiologia , Nasofaringe/patologia , Nasofaringe/cirurgia , Traqueia/microbiologia , Traqueia/patologia , Traqueia/cirurgia , Resultado do Tratamento , Voriconazol/farmacologia , Voriconazol/uso terapêutico
9.
Pestic Biochem Physiol ; 163: 1-7, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31973844

RESUMO

Botrytis cinerea isolates with multi-fungicide resistance have frequently been isolated from small fruit fields such as strawberries and blackberries. Individual B. cinerea isolates have been found resistant to up to seven chemical classes of fungicides. Fitness costs and less competitiveness have been observed in multi-fungicide resistant isolates, but this has not been examined under field conditions. In the spring of 2016, flowers of field-grown blackberries were either not inoculated or inoculated with B. cinerea isolates sensitive (0CCR), resistant to five or six chemical classes excluding phenylpyrroles (5CCR), or resistant to six or seven chemical classes including phenylpyrroles (6CCR/MDR1h). The experimental field was left unsprayed for the duration of this study and isolates of B. cinerea were collected from flowers and/or fruit in each of the three experimental years. Isolates collected in summer of 2016 revealed resistance phenotypes in each plot closely matching those of the respective inoculum, with 95% 0CCR, 55% 5CCR, and 91% 6CCR/MDR1h isolates recovered from 0CCR, 5CCR, and 6CCR/MDR1h inoculation plots, respectively. In the 2017 and 2018 isolate collections, 6CCR/MDR1h resistance phenotypes were found in plots inoculated and non-inoculated with this phenotype, indicating their persistence and movement between plots. Resistance phenotypes different from the inoculum were also recovered each year, indicating that the inoculum was successfully competing with a native Botrytis population. Despite the competition, 6CCR/MDR1h isolates were recovered in high frequency from all inoculated plots in 2018. G3pdh and mrr1 sequences of 6CCR/MDR1h isolates collected in 2018 were identical to the sequences of the inoculum, indicating that these isolates likely descended from the inoculum. This study demonstrates that isolates carrying multi-fungicide resistant phenotypes, specifically 6CCR/MDR1h, are competitive in the absence of fungicide selection pressure.


Assuntos
Fungicidas Industriais , Rubus , Botrytis , Farmacorresistência Fúngica , Doenças das Plantas
10.
Environ Pollut ; 256: 113385, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31662261

RESUMO

Triazole resistance in Aspergillus fumigatus is a major cause of clinical inefficacy in the treatment of invasive aspergillosis (IA). The hypothesis that triazole fungicides have driven the development of resistance in A. fumigatus has garnered substantial attention due to the similar structure and global detection of antifungal resistant A. fumigatus (ARAF) isolates in the soil. However, there is little evidence linking the application of triazole fungicides to the emergence of ARAF in the soil. This study was conducted to test if the resistance in A. fumigatus and its associated mutations in cyp51A could be induced by propiconazole in liquid medium and soil. The results indicate that propiconazole can induce resistance by alteration of G138S in cyp51A, and the overexpression of cyp51A, AfuMDR3 and AfuMDR4. G138S in cyp51A was first detected in the soil and associated with resistance. The emergence of the ARAFs in the soil may depends upon the level of propiconazole, and the number of ARAFs in soil treated with propiconazole at 2- and 5-fold dose was much greater than those in soil treated at the recommended dosage. The current data indicate that propiconazole can induce triazole resistance in A. fumigatus and should be applied for agricultural purposes at levels at or below the recommended dosage to avoid the emergence of ARAF in the soil.


Assuntos
Antifúngicos/toxicidade , Aspergillus fumigatus/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/genética , Triazóis/toxicidade , Aspergillus fumigatus/genética , Farmacorresistência Fúngica/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Solo/química , Microbiologia do Solo , Soluções
11.
Phytopathology ; 110(3): 615-625, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31799899

RESUMO

Colletotrichum spp. isolates contain two paralogous CYP51 genes that encode sterol 14-demethylase enzymes; however, their role in sensitivity to demethylation inhibitor (DMI) fungicides is yet to be determined. In this study, each of the two genes from Colletotrichum fioriniae and C. nymphaeae was able to rescue the function of CYP51 in the yeast Saccharomyces cerevisiae, demonstrating their independent function. Deletion of CYP51A led to increased sensitivity to propiconazole, diniconazole, prothioconazole, cyproconazole, epoxiconazole, flutriafol, prochloraz, and difenoconazole in C. fioriniae, and to the same fungicides and tebuconazole in C. nymphaeae, with the exception of prochloraz. Deletion of CYP51B in C. fioriniae and CYP51B in C. nymphaeae made mutants increasingly sensitive to five of nine DMI fungicides tested. The results suggest species-specific, differential binding of DMI fungicides onto the two CYP51 enzymes. Pairing DMIs with different effects on CYP51A and -B deletion mutants resulted in synergistic effects, as determined in mycelial growth inhibition experiments. Deletion mutants showed no fitness penalty in terms of mycelial growth, sporulation, and virulence. Our study elucidates the effect of CYP51A and CYP51B of Colletotrichum spp. on DMI sensitivity, suggesting that using a mixture of DMIs may improve the efficacy for anthracnose management.


Assuntos
Colletotrichum , Fungicidas Industriais , Desmetilação , Farmacorresistência Fúngica , Doenças das Plantas , Esterol 14-Desmetilase , Esteróis
12.
Plant Dis ; 104(1): 211-221, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765279

RESUMO

Phytophthora infestans is the causal agent of late blight disease of potatoes and tomatoes. This disease causes devastating economic losses each year, and control is mainly achieved by the use of fungicides. Unfortunately, populations of P. infestans resistant to fungicides have been documented. Furthermore, studies have reported that sensitive isolates to the phenylamide fungicide, mefenoxam, become less sensitive in vitro after a single passage through sublethal concentrations of fungicide-amended medium. The first objective of this study was to investigate if isolates of P. infestans are capable of acquiring resistance to two additional systemic fungicides, fluopicolide (benzamide) and cymoxanil (cyanoacetamide-oxime). In contrast to the situation with mefenoxam, exposure of isolates to sublethal concentrations of fluopicolide and cymoxanil did not induce reduced sensitivity to these two fungicides. The second objective was to assess if reduced sensitivity to mefenoxam could occur in naturally sensitive isolates of other Phytophthora species and of Phytopythium sp., another oomycete plant pathogen. All Phytophthora spp. assessed (P. infestans, P. betacei, and P. pseudocryptogea) as well as Phytopythium sp. acquired resistance to mefenoxam after previous exposure through medium containing 1 µg ml-1 of mefenoxam. Interestingly, isolate 66 of Phytopythium sp. and the isolate of P. pseudocryptogea tested do not seem to be acquiring resistance to mefenoxam after exposure to medium containing 5 µg ml-1 of this fungicide. The tested isolates of P. palmivora and P. cinnamomi were extremely sensitive to mefenoxam, and thus it was not possible to perform a second transfer to access acquisition of resistance to this fungicide.


Assuntos
Alanina/análogos & derivados , Farmacorresistência Fúngica , Phytophthora infestans , Alanina/farmacologia , Fungicidas Industriais/farmacologia , Phytophthora infestans/efeitos dos fármacos , Solanum tuberosum/microbiologia
13.
Plant Dis ; 104(2): 306-314, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31804902

RESUMO

Alternaria late blight (ALB) caused by Alternaria spp. is an annual disease problem in California pistachio and requires repeated applications of fungicides to prevent significant losses of pistachio foliage and nut quality. From 2003 onward, the succinate dehydrogenase inhibiting fungicide boscalid has played a key role in ALB management. The development of boscalid resistance in A. alternata populations was monitored from 2005 to 2012 in pistachio producing areas in California. A total of 1,765 single-spore isolates, collected from commercial and experimental pistachio orchards with or without a history of boscalid exposure, were tested in a radial growth assay in agar media amended with the discriminatory dose of 10 µg/ml of boscalid. The frequency of boscalid-resistant isolates in 2005 was 12% but increased significantly and remained stable toward the end of the survey period. Most of the resistant isolates exhibited a high level of resistance (R) to boscalid with percent of mycelial growth inhibition (PGI) values between 0 and 50%, whereas significantly fewer isolates had an intermediate level (IR) of resistance (50 < PGI < 75%). The frequency of sensitive (S) isolates (75 < PGI < 100%) was generally the highest in orchards with no history of boscalid usage, whereas mean incidences of boscalid-resistant populations of Alternaria were 81, 92.4, 80.2, and 98%, in 2006, 2007, 2011, and 2012, respectively, in orchards that received a high number (at least three per season) of boscalid spray applications. In comparison, none to relatively low frequencies (0 to 12%) of resistance were observed in populations with no or limited exposure to Pristine, suggesting an air-movement of resistant spores through wind from treated to nontreated areas. In 2012, boscalid-resistant isolates were found practically in every sampled location in all counties, with the orchards in Fresno, Madera, Tulare, and King Counties being the locations with the highest frequencies of resistance (100%). Monitoring of A. alternata AaSDHB, AaSDHC, and AaSDHD mutations in 286 boscalid-resistant phenotypes identified 11 mutations, leading to amino acid substitutions in AaSDHB (seven mutations: H277Y/R/L, P230A/R, N235D/T), AaSDHC (one mutation: H134R), and AaSDHD (three mutations: D123E, H133R/P), with AaSDHB mutations being the most prevalent (80%) ones throughout the survey period. The majority of isolates carrying these mutations exhibited the R phenotype toward boscalid. The increased prevalence of boscalid resistance in populations of A. alternata is a likely contributing factor to the inability of pistachio farmers to successfully control ALB with Pristine. Other factors implicated in the rapid and widespread occurrence of A. alternata boscalid-resistant populations in California pistachios are further discussed.


Assuntos
Alternaria , Pistacia , Compostos de Bifenilo , California , Farmacorresistência Fúngica , Niacinamida/análogos & derivados
14.
Phytopathology ; 110(2): 327-335, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31502521

RESUMO

Succinate dehydrogenase inhibitors (SDHIs) are an essential group of fungicides for managing gray mold, caused by Botrytis cinerea, in numerous crops. Resistance to boscalid, an early-generation SDHI, is widespread worldwide and was linked to mutations in the iron-sulfur protein encoding the SdhB subunit of the SDH complex. Herein, we report on four simultaneous dependent mutations at codons 85 (G85A), 93 (I93V), 158 (M158V), and 168 (V168I) of the membrane-anchored SdhC subunit of B. cinerea. Isolates without and with mutations in SdhC were referred to as C- and C+ genotypes, respectively. The C+ genotype was found in all the five surveyed hosts from different U.S. regions but its frequency was higher, 25 to 40%, in the tree fruit isolates compared with 12 to 25% in the small fruit populations. The four SdhC mutations were found in isolates without mutations in SdhB or with mutations known to confer resistance to the SDHIs in SdhB. However, the frequency of C+ isolates was significantly higher in the SdhB wild-type isolates, which suggests that SDHI sprays may have played a role in selecting for the C- over the C+ genotype. Field C+ isolates exhibited reduced sensitivity to fluopyram and increased sensitivity to boscalid and penthiopyrad in vitro and on detached fruit. Homology modeling confirmed the positioning of the four mutations in the ubiquinone-binding pocket. The SdhCG85A is found in the proximal ubiquinone binding site and SdhCM158V is positioned in the iron sulfur protein interface next to the [3Fe-4S] cluster, whereas SdhCI93V is positioned next to the heme b with vital functions in the SDH enzyme. Beside the differential sensitivity to the SDHIs, these mutations caused a significant fitness cost in the C+ isolates including sporulation and increased sensitivity to reactive oxygen species. The presence of Botrytis populations differentially sensitive to the SDHIs suggests increased risks for resistance development but also opens up new perspective for future gray mold management using different SDHI fungicides.


Assuntos
Proteínas de Bactérias , Botrytis , Inibidores Enzimáticos , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Botrytis/efeitos dos fármacos , Botrytis/genética , Farmacorresistência Fúngica , Inibidores Enzimáticos/farmacologia , Frutas/microbiologia , Fungicidas Industriais , Genótipo , Mutação , Doenças das Plantas/microbiologia
15.
Sci Total Environ ; 703: 135557, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31767318

RESUMO

Combating drug-resistance is a daunting task, especially due to the shortage of available drug alternatives with multisite modes of action. In this study, the potential of copper nanoparticles (Cu-NPs) to suppress 15 Botrytis cinerea isolates, which are sensitive or resistant to fungicides, alone or in combination with conventional fungicides, was tested in vitro and in vivo. Sensitivity screening in vitro revealed two fungicide resistance phenotypes, resulting from target site mutations. DNA sequencing revealed three B. cinerea isolates highly resistant to benzimidazoles (BEN-R), thiophanare methyl (TM), and carbendazim, bearing the E198A resistance mutation in the ß-tubulin gene, and four isolates highly resistant to the QoI pyraclostrobin (PYR-R) with a G143A mutation in the cytb gene. Cu-NPs were equally effective against sensitive and resistant isolates. An additive/synergistic effect was observed between Cu-NPs and TM in the case of BEN-S isolates both in vitro and when applied in apple fruit. A positive correlation was observed between TM and TM + Cu-NPs treatments, suggesting that an increased TM availability in the target site could be related with the observed additive/synergistic action. No correlation between Cu(OH)2 and Cu-NPs sensitivity was found, indicating that different mechanisms govern the fungitoxic activity between nano and bulk counterparts. A synergistic profile was observed between Cu-NPs and fluazinam (FM) - an oxidative phosphorylation inhibitor - in all isolates regardless of resistance phenotype, suggesting that ATP metabolism could be involved in the mode of action of Cu-NPs. Furthermore, the observed cross sensitivity and antagonistic action between Cu-NPs and NaCl also provided evidence for copper ions contribution to the fungitoxic action of Cu-NPs. The results suggested that Cu-NPs in combination with conventional fungicides can provide the means for an environmentally safe, sustainable resistance management strategy by reducing fungicide use and combating resistance against B. cinerea.


Assuntos
Botrytis/efeitos dos fármacos , Cobre/química , Farmacorresistência Fúngica/efeitos dos fármacos , Nanopartículas Metálicas/química , Benzimidazóis , Carbamatos , Nanopartículas Metálicas/toxicidade , Fenótipo , Doenças das Plantas
16.
Plant Dis ; 104(1): 129-136, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31747352

RESUMO

Gummy stem blight, caused by Stagonosporopsis spp., is a major disease of cucurbits in the United States and China that is managed primarily through the use of fungicides. The objective of this study was to monitor and compare the recent fungicide resistance profiles of Stagonosporopsis spp. in Florida open-field and East China protected-structure production systems. Isolates of Stagonosporopsis spp. were evaluated for sensitivity to the commonly used fungicides azoxystrobin, boscalid, tebuconazole, and thiophanate-methyl at discriminatory rates of 0.096, 0.034, 0.128, and 100 mg/liter, respectively. Isolates were collected from Jiangsu, Jiangxi, Zhejiang, and Anhui provinces in China (n = 69), 12 counties in Florida (n = 89), and one county in Georgia (n = 6). More than 50% of isolates from Florida and East China were resistant to thiophanate-methyl. Boscalid resistance was detected in both isolate collections but was two times more frequent in China. Resistance to azoxystrobin was detected in 66% of isolates in Florida but only 7% in China. Tebuconazole was effective in controlling the mycelia growth of Stagonosporopsis spp. in both collections. The results indicate that both production systems currently face similar challenges related to the development of fungicide resistance in Stagonosporopsis spp. However, the resistance profiles are unique for both production systems.


Assuntos
Agricultura , Ascomicetos , Cucurbita , Farmacorresistência Fúngica , Fungicidas Industriais , Agricultura/tendências , Ascomicetos/efeitos dos fármacos , China , Cucurbita/microbiologia , Florida , Fungicidas Industriais/farmacologia , Georgia , Doenças das Plantas/microbiologia
17.
Ecotoxicol Environ Saf ; 187: 109868, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31689623

RESUMO

The occurrence of azole antifungals in the environment presents one of the emerging concerns due to their ecotoxicological threat as well as their potential contribution to the evolution of drug resistant fungi in the environment. In this study, the occurrence of eight commonly prescribed azole antifungal drugs was seasonally determined in influent and effluent water samples from three wastewater treatment plants and a drinking water treatment plant in South Africa. In addition, the risk quotient (RQ) method was employed to investigate the potential ecological and human health risks associated with their presence in the wastewater and/or drinking water. Clotrimazole, econazole, fluconazole, itraconazole, ketoconazole and miconazole were detected at least once in the water samples, while posaconazole and voriconazole were not detected in any of the samples for all seasons at which the samples were collected. Fluconazole was detected at higher frequency (about 96%) with a concentration up to 9959.0 ng L-1. Clotrimazole had the second highest frequency of detection (about 33%) with a concentration up to 143.3 ng L-1. Statistically significant temporal variation in clotrimazole (p < 0.05) and spatial variation in fluconazole (p < 0.05) were observed. In general, the preliminary ecological risk assessment based on risk quotient (RQ) calculation indicated that there is currently no high risk against aquatic organisms (Algae, Daphnia and Fish) related to the azole antifungals. Meanwhile, human health risk assessment demonstrated that fluconazole represented high risk in drinking water. Furthermore, risk estimates showed a potential for the detected concentrations of fluconazole and itraconazole in water samples to pose moderate to high risk for development of antifungal drug resistance. Some of the azole antifungal drugs are ubiquitous in the wastewater and future monitoring and validation studies should be conducted for those drugs that seem to pose human health and ecological risks.


Assuntos
Antifúngicos/análise , Azóis/análise , Água Potável/química , Monitoramento Ambiental/métodos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Antifúngicos/toxicidade , Organismos Aquáticos/efeitos dos fármacos , Azóis/toxicidade , Farmacorresistência Fúngica , Ecotoxicologia , Humanos , Medição de Risco , África do Sul , Poluentes Químicos da Água/toxicidade
18.
Pestic Biochem Physiol ; 162: 60-68, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31836056

RESUMO

Stem-end rot caused by Lasiodiplodia theobromae is one of the most devastating diseases of papaya in northeastern Brazil. It is most effectively controlled by applications of fungicides, including site-specific fungicides at risk for resistance development. This study investigated the molecular mechanisms of reduced sensitivity to the QoI fungicide azoxystrobin and resistance to the MBC fungicide thiophanate-methyl in L. theobromae from Brazilian orchards. The EC50 values for azoxystrobin in sixty-four isolates ranged from 0.36 µg/ml to 364.24 µg/ml and the frequency distribution of EC50 values formed a multimodal curve, indicating reduced sensitivity to azoxystrobin. In detached fruit assays reduced sensitive isolates were not controlled as effectively as sensitive isolates at lowest label rate. Partial fragments were obtained from target genes ß-tubulin (751 bp) and Cytb (687 bp) of isolates resistant to thiophanate-methyl and reduced sensitivity to azoxystrobin. Sequence analysis of the ß-tubulin fragment revealed a mutation corresponding to E198K in all thiophanate-methyl-resistant isolates, while reduced sensitivity to axoxystrobin was not attributable to Cytb gene alterations. The target gene-based mechanism conferring resistance to thiophanate-methyl will likely be stable even if selection pressure subsides. However, the mechanism conferring reduced sensitivity to azoxystrobin is not based on target gene modifications and thus may not be as stable as other genotypes with mutations in Cytb gene.


Assuntos
Ascomicetos , Carica , Fungicidas Industriais , Brasil , Farmacorresistência Fúngica , Pirimidinas , Estrobilurinas , Tiofanato
19.
Biosci Biotechnol Biochem ; 84(1): 198-207, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31566090

RESUMO

High glycosidase-producing strains of Aspergillus luchuensis were isolated from 2-deoxyglucose (2-DG) resistant mutants. α-Amylase, exo-α-1,4-glucosidase, ß-glucosidase and ß-xylosidase activity in the mutants was ~3, ~2, ~4 and ~2.5 times higher than the parental strain RIB2604 on koji-making conditions, respectively. Citric acid production and mycelia growth of the mutants, however, approximately halved to that of the parent. Compared to the parent, the alcohol yield from rice and sweet potato shochu mash of the mutant increased ~5.7% and 3.0%, respectively. The mutant strains showed significantly low glucose assimilability despite the fructose one was almost normal, and they had a single missense or nonsense mutation in the glucokinase gene glkA. The recombinant strain that was introduced at one of the mutations, glkA Q300K, demonstrated similar but not identical phenotypes to the mutant strain. This result indicates that glkA Q300K is one of the major mutations in 2-DG resistant strains.


Assuntos
Aspergillus/genética , Aspergillus/isolamento & purificação , Separação Celular/métodos , Códon sem Sentido/genética , Genes Fúngicos/genética , alfa-Glucosidases/metabolismo , Aspergillus/classificação , Aspergillus/metabolismo , Catepsina A/metabolismo , Ácido Cítrico/metabolismo , Desoxiglucose/farmacologia , Farmacorresistência Fúngica , Etanol/metabolismo , Fermentação , Frutose/metabolismo , Glucoquinase/genética , Glucose/metabolismo , Ipomoea batatas/química , Oryza/química , Fenótipo , Saccharomyces cerevisiae/classificação , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/isolamento & purificação , Saccharomyces cerevisiae/metabolismo , Xilosidases/metabolismo , alfa-Amilases/metabolismo , beta-Glucosidase/metabolismo
20.
Chem Commun (Camb) ; 55(100): 15145-15148, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31790115

RESUMO

A lipase-triggered drug release nanoplatform (PGL-DPP-FLU NPs) for multi-modal antifungal therapy is developed. The lipases secreted by C. albicans can accelerate FLU release. The ROS and heat produced by PGL-DPP-FLU NPs make C. albicans more vulnerable to FLU, thereby PGL-DPP-FLU NPs exhibit high performance for combating azole-resistant C. albicans biofilms and wound infection.


Assuntos
Antifúngicos/farmacologia , Azóis/química , Candida albicans/efeitos dos fármacos , Lipase/metabolismo , Nanopartículas/química , Animais , Antifúngicos/química , Antifúngicos/uso terapêutico , Azóis/farmacologia , Candidíase/tratamento farmacológico , Candidíase/patologia , Candidíase/veterinária , Farmacorresistência Fúngica/efeitos dos fármacos , Etilenoglicóis/química , Fluconazol/química , Cetonas/química , Lasers , Camundongos , Fotoquimioterapia , Fototerapia , Poliésteres/química , Pirróis/química
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