scholarly journals Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides

2017 ◽  
Vol 284 (1863) ◽  
pp. 20170635 ◽  
Author(s):  
Jianhua Zhang ◽  
Joost van den Heuvel ◽  
Alfons J. M. Debets ◽  
Paul E. Verweij ◽  
Willem J. G. Melchers ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Selection Pressure ◽  
Target Genes ◽  
Evolutionary Dynamics ◽  
Resistance Mechanism ◽  
Cross Resistance ◽  
Resistance Selection ◽  
Patients At Risk ◽  
Selection Of ◽  
Selection Of Resistance

Resistance to medical triazoles in Aspergillus fumigatus is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through selection pressure from non-medical sterol-biosynthesis-inhibiting (SI) triazole fungicides which are used in the environment. Previous studies have suggested that SI fungicides can induce cross-resistance to medical triazoles. Therefore, to assess the potential of selection of resistance to medical triazoles in the environment, we assessed cross-resistance to three medical triazoles in lineages of A. fumigatus from previous work where we applied an experimental evolution approach with one of five different SI fungicides to select for resistance. In our evolved lines we found widespread cross-resistance indicating that resistance to medical triazoles rapidly arises through selection pressure of SI fungicides. All evolved lineages showed similar evolutionary dynamics to SI fungicides and medical triazoles, which suggests that the mutations inducing resistance to both SI fungicides and medical triazoles are likely to be the same. Whole-genome sequencing revealed that a variety of mutations were putatively involved in the resistance mechanism, some of which are in known target genes.

Section 8. Pyrethroid resistance: field resistance mechanisms

1993 ◽  
Vol 1 ◽  
pp. 54-61 ◽  
Author(s):  
Neil W. Forrester ◽  
Matthew Cahill ◽  
Lisa J. Bird ◽  
Jacquelyn K. Layland
Keyword(s):  
Selection Pressure ◽  
Pyrethroid Resistance ◽  
Life Stage ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Field Resistance ◽  
Monooxygenase System ◽  
Phenotypic Resistance ◽  
Nectar Feeding ◽  
Selection Of

SummaryThe dual insecticide ± synergist discriminating dose technique proved highly successful in determining the relative importance of pyrethroid resistance mechanisms present in field populations of Helicoverpa armigera, without the problems of alternative techniques. Synergist pre-treatment proved unnecessary therefore allowing use of the more convenient and labour efficient discriminating dose pre-mix.Oxidative metabolic detoxification, probably via a polysubstrate monooxygenase system, was the major pyrethroid resistance mechanism in both larval and adult H. armigera. Residual piperonyl butoxide insensitive resistance (presumably nerve insensitivity, possibly acting in combination with the penetration resistance factor) was also present but at a low level. This latter resistance mechanism was expressed in larvae but moths appeared to express only weak phenotypic resistance. The predominant pyrethroid resistance mechanism employed by insects is discussed in relation to their feeding habit. The tenet that nectar feeding adult Lepidoptera are unable to express metabolic pyrethroid resistance is challenged.Unrestrained pre-strategy pyrethroid selection pressure on sequential generations resulted in selection for elevated levels of kdr type nerve insensitivity and possibly even super kdr. Restriction of pyrethroid selection pressure to one generation per season favoured selection of the oxidative over the nerve insensitivity resistance mechanism. Two possibly complementary explanations are put forward for this; differential genetic dominance (semidominant oxidative mechanism versus recessive nerve insensitivity) and/or selection in more than one life stage (moths and larvae for the oxidative mechanism versus predominantly larvae only for the nerve insensitivity mechanism). It is suggested that insecticide resistance management strategies should be designed to avoid selection of elevated levels of the intractable nerve insensitivity resistance mechanism whereas low levels of this mechanism (normal kdr) are not considered difficult to manage. The demonstration that the strategy has favoured selection of the more amenable oxidative resistance mechanism invites the opportunity to develop possible chemical countermeasures.

scholarly journals In Vitro Selection of Resistance to Four β-Lactams and Azithromycin in Streptococcus pneumoniae

1998 ◽  
Vol 42 (11) ◽  
pp. 2914-2918 ◽  
Author(s):  
Glenn A. Pankuch ◽  
Shane A. Jueneman ◽  
Todd A. Davies ◽  
Michael R. Jacobs ◽  
Peter C. Appelbaum
Keyword(s):  
Streptococcus Pneumoniae ◽  
In Vitro Selection ◽  
Antimicrobial Agents ◽  
Penicillin G ◽  
Resistance Selection ◽  
Resistant Strains ◽  
Selection Of ◽  
Selection Of Resistance

ABSTRACT Selection of resistance to amoxicillin (with or without clavulanate), cefaclor, cefuroxime, and azithromycin among six penicillin G- and azithromycin-susceptible pneumococcal strains and among four strains with intermediate penicillin sensitivities (azithromycin MICs, 0.125 to 4 μg/ml) was studied by performing 50 sequential subcultures in medium with sub-MICs of these antimicrobial agents. For only one of the six penicillin-susceptible strains did subculturing in medium with amoxicillin (with or without clavulanate) lead to an increased MIC, with the MIC rising from 0.008 to 0.125 μg/ml. Five of the six penicillin-susceptible strains showed increased azithromycin MICs (0.5 to >256.0 μg/ml) after 17 to 45 subcultures. Subculturing in medium with cefaclor did not affect the cefaclor MICs of three strains but and led to increased cefaclor MICs (from 0.5 to 2.0 to 4.0 μg/ml) for three of the six strains, with MICs of other β-lactams rising 1 to 3 twofold dilutions. Subculturing in cefuroxime led to increased cefuroxime MICs (from 0.03 to 0.06 μg/ml to 0.125 to 0.5 μg/ml) for all six strains without significantly altering the MICs of other β-lactams, except for one strain, which developed an increased cefaclor MIC. Subculturing in azithromycin did not affect β-lactam MICs. Subculturing of the four strains with decreased penicillin susceptibility in amoxicillin (with or without clavulanate) or cefuroxime did not select for β-lactam resistance. Subculturing of one strain in cefaclor led to an increase in MIC from 0.5 to 2.0 μg/ml after 19 passages. In contrast to strains that were initially azithromycin susceptible, which required >10 subcultures for resistance selection, three of four strains with azithromycin MICs of 0.125 to 4.0 μg/ml showed increased MICs after 7 to 13 passages, with the MICs increasing to 16 to 32 μg/ml. All azithromycin-resistant strains were clarithromycin resistant. With the exception of strains that contained mefE at the onset, no strains that developed resistance to azithromycin containedermB or mefE, genes that have been found in macrolide-resistant pneumococci obtained from clinic patients.

scholarly journals Environmental Hotspots for Azole Resistance Selection of Aspergillus fumigatus, the Netherlands

2019 ◽  
Vol 25 (7) ◽  
pp. 1347-1353 ◽  
Author(s):  
Sijmen E. Schoustra ◽  
Alfons J.M. Debets ◽  
Antonius J.M.M. Rijs ◽  
Jianhua Zhang ◽  
Eveline Snelders ◽  
...  
Keyword(s):  
The Netherlands ◽  
Aspergillus Fumigatus ◽  
Azole Resistance ◽  
Resistance Selection ◽  
Selection Of

scholarly journals Understanding the Resistance Mechanism in Brassica napus to Clubroot Caused by Plasmodiophora brassicae

2019 ◽  
Vol 109 (5) ◽  
pp. 810-818 ◽  
Author(s):  
Jiaqin Mei ◽  
Zhen Guo ◽  
Jinhua Wang ◽  
Yuxia Feng ◽  
Guanhua Ma ◽  
...  
Keyword(s):  
Brassica Napus ◽  
Plasmodiophora Brassicae ◽  
Resistance Mechanism ◽  
Oxygen Species ◽  
Rna Seq ◽  
Receptor Kinases ◽  
Rapeseed Cultivar ◽  
Root Hair Infection ◽  
Selection Of ◽  
Selection Of Resistance

Exploring the mechanism of plant resistance has become the basis for selection of resistance varieties but reports on revealing resistant mechanism in Brassica napus against Plasmodiophora brassicae are rare. In this study, RNA-seq was conducted in the clubroot-resistant B. napus breeding line ZHE-226 and in the clubroot-susceptible rapeseed cultivar Zhongshuang 11 at 0, 3, 6, 9, and 12 days after inoculation. Strong alteration was detected specifically in ZHE-226 as soon as the root hair infection happened, and significant promotion was found in ZHE-226 on cell division or cell cycle, DNA repair and synthesis, protein synthesis, signaling, antioxidation, and secondary metabolites. Combining results from physiological, biochemical, and histochemical assays, our study highlights an effective signaling in ZHE-226 in response to P. brassicae. This response consists of a fast initiation of receptor kinases by P. brassicae; the possible activation of host intercellular G proteins which might, together with an enhanced Ca2+ signaling, promote the production of reactive oxygen species; and programmed cell death in the host. Meanwhile, a strong ability to maintain homeostasis of auxin and cytokinin in ZHE-226 might effectively limit the formation of clubs on host roots. Our study provides initial insights into resistance mechanism in rapeseed to P. brassicae.

scholarly journals Neonicotinoid and pyrethroid combination: A tool to manage insecticide resistance in malaria vectors? Insights from experimental evolution

2021 ◽  
Author(s):  
Marius Gonse Zoh ◽  
Jean-Marc Bonneville ◽  
Jordan Tutagana ◽  
Frederic Laporte ◽  
Behi Kouadio Fodjo ◽  
...  
Keyword(s):  
Public Health ◽  
Insecticide Resistance ◽  
Vector Control ◽  
Target Site ◽  
Cross Resistance ◽  
Site Mutation ◽  
Selection Signature ◽  
The Impact ◽  
Selection Of ◽  
Selection Of Resistance

Background: The introduction of neonicotinoids for managing insecticide resistance in mosquitoes is of high interest as they interact with a biochemical target not previously used in public health. In this concern, Bayer developed a combination of the neonicotinoid clothianidin and the pyrethroid deltamethrin (brand name Fludora Fusion) as a new vector control tool. Although this combination proved to be efficient against pyrethroid-resistant mosquitoes, its ability to prevent the selection of pyrethroid and neonicotinoid resistance alleles was not investigated. In this context, the objective of this work was to study the dynamics and the molecular mechanisms of resistance of An. gambiae to the separated or combined components of this combination. A field-derived An. gambiae line carrying resistance alleles to multiple insecticides at low frequencies was used as a starting for 33 successive generations of controlled selection. Resistance levels to each insecticide and target site mutation frequencies were monitored throughout the selection process. Cross resistance to other public health insecticides were also investigated. RNA-seq was used to compare gene transcription variations and polymorphisms across all lines. Results: This study confirmed the potential of this insecticide combination to impair the selection of resistance as compared to its two separated components. Deltamethrin selection led to the rapid enrichment of the kdr L1014F target-site mutation while clothianidin selection led to the over-transcription of multiple cytochrome P450s including some showing high homology with the ones conferring neonicotinoid resistance in other insects. A strong selection signature associated with clothianidin selection was observed on a cytochrome P450 gene cluster previously associated with resistance. Within this cluster, the gene CYP6M1 showed the highest selection signature together with a transcription profile supporting a role in clothianidin resistance. Modelling the impact of point mutations selected by clothianidin on CYP6M1 protein structure suggested that the selection of variants affecting its active site can enhance clothianidin metabolism. Conclusions: In the context of the recent deployment of neonicotinoids for mosquito control and their frequent usage in agriculture, the present study highlights the benefit of combining them with other insecticides for preventing the selection of resistance and sustaining vector control activities.

scholarly journals Possible Environmental Origin of Resistance of Aspergillus fumigatus to Medical Triazoles

2009 ◽  
Vol 75 (12) ◽  
pp. 4053-4057 ◽  
Author(s):  
Eveline Snelders ◽  
Robert A. G. Huis in 't Veld ◽  
Anthonius J. M. M. Rijs ◽  
Gert H. J. Kema ◽  
Willem J. G. Melchers ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Genetic Relatedness ◽  
Antifungal Susceptibility ◽  
Resistance Mechanism ◽  
Outdoor Environment ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Cross Resistance ◽  
Natural Soil ◽  
Plant Nursery

ABSTRACT We reported the emergence of resistance to medical triazoles of Aspergillus fumigatus isolates from patients with invasive aspergillosis. A dominant resistance mechanism was found, and we hypothesized that azole resistance might develop through azole exposure in the environment rather than in azole-treated patients. We investigated if A. fumigatus isolates resistant to medical triazoles are present in our environment by sampling the hospital indoor environment and soil from the outdoor environment. Antifungal susceptibility, resistance mechanisms, and genetic relatedness were compared with those of azole-resistant clinical isolates collected in a previous study. Itraconazole-resistant A. fumigatus (five isolates) was cultured from the indoor hospital environment as well as from soil obtained from flower beds in proximity to the hospital (six isolates) but never from natural soil. Additional samples of commercial compost, leaves, and seeds obtained from a garden center and a plant nursery were also positive (four isolates). Cross-resistance was observed for voriconazole, posaconazole, and the azole fungicides metconazole and tebuconazole. Molecular analysis showed the presence of the dominant resistance mechanism, which was identical to that found in clinical isolates, in 13 of 15 environmental isolates, and it showed that environmental and clinical isolates were genetically clustered apart from nonresistant isolates. Patients with azole-resistant aspergillosis might have been colonized with azole-resistant isolates from the environment.

scholarly journals A New Aspergillus fumigatus Resistance Mechanism Conferring In Vitro Cross-Resistance to Azole Antifungals Involves a Combination of cyp51A Alterations

2007 ◽  
Vol 51 (6) ◽  
pp. 1897-1904 ◽  
Author(s):  
E. Mellado ◽  
G. Garcia-Effron ◽  
L. Alcázar-Fuoli ◽  
W. J. G. Melchers ◽  
P. E. Verweij ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Tandem Repeat ◽  
Wild Type Strain ◽  
Resistance Mechanism ◽  
Cross Resistance ◽  
Wild Type ◽  
Azole Antifungals ◽  
Quantitative Expression ◽  
Resistant Phenotype

ABSTRACT Fourteen Aspergillus fumigatus clinical isolates that exhibited a pattern of reduced susceptibility to triazole drugs were analyzed. The sequences of the cyp51A gene from all isolates showed the presence of a point mutation at t364a, which led to the substitution of leucine 98 for histidine (L98H), together with the presence of two copies of a 34-bp sequence in tandem in the promoter of the cyp51A gene. Quantitative expression analysis (real-time PCR) showed up to an eightfold increase in the level of expression of the cyp51A gene compared to that by the susceptible strain. Three PCR fragments of one azole-resistant strain (strain CM2627) that included the promoter with the tandem repeat and part of cyp51A with the t364a mutation or PCR fragments with only one of the modifications were used to replace the cyp51A gene of an azole drug-susceptible A. fumigatus wild-type strain (strain CM237). Only transformants which had incorporated the tandem repeat in the promoter of the cyp51A gene and the L98H amino acid substitution exhibited similarly reduced patterns of susceptibility to all triazole agents and similarly increased levels of cyp51A expression, confirming that the combination of both alterations was responsible for the azole-resistant phenotype.

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