Section 3. Evaluation of the impact of the strategy on pyrethroid resistance: F1 analyses

1993 ◽  
Vol 1 ◽  
pp. 21-27
Author(s):  
Neil W. Forrester ◽  
Matthew Cahill ◽  
Lisa J. Bird ◽  
Jacquelyn K. Layland
Keyword(s):  
Pyrethroid Resistance ◽  
Resistance Mechanism ◽  
Resistance Management ◽  
Resistance Mechanisms ◽  
Field Resistance ◽  
Relative Importance ◽  
Oxidative Resistance ◽  
Tolerance Curve ◽  
The Impact ◽  
Selection Of

SummaryThe classical resistance monitoring technique using full bioassay lines on laboratory reared F1 progeny of field material was compared to the previously described discriminating dose technique on field collected individuals. The Via tolerance curve analysis of the F1 data clearly indicated the predominance of the oxidative metabolic pyrethroid resistance mechanism from the 1984/85 season onwards. There appears to have been an abrupt change in the relative importance of field resistance mechanisms following the introduction of the insecticide resistance management (IRM) strategy in 1983/84. The strategy seems to have favoured the selection of the more amenable oxidative resistance mechanism over the intractable nerve insensitivity mechanism. The Beeman-Nanis analysis was applied to attempt to identify the relative importance of the various field resistance genes. However, it proved of little value in this study as one of the key assumptions underlying the analysis (full genetic dominance) was not satisfied.

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 Playing the Whack-A-Mole Game: ERK5 Activation Emerges Among the Resistance Mechanisms to RAF-MEK1/2-ERK1/2- Targeted Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Alessandro Tubita ◽  
Ignazia Tusa ◽  
Elisabetta Rovida
Keyword(s):  
Tyrosine Kinases ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Therapies ◽  
New Era ◽  
Mitogen Activated Protein ◽  
The Impact ◽  
The Ideal

Molecularly tailored therapies have opened a new era, chronic myeloid leukemia being the ideal example, in the treatment of cancer. However, available therapeutic options are still unsatisfactory in many types of cancer, and often fail due to the occurrence of resistance mechanisms. With regard to small-molecule compounds targeting the components of the Mitogen-Activated Protein Kinase (MAPK) cascade RAF-MEK1/2-ERK1/2, these drugs may result ineffective as a consequence of the activation of compensatory pro-survival/proliferative signals, including receptor tyrosine kinases, PI3K, as well as other components of the MAPK family such as TPL2/COT. The MAPK ERK5 has been identified as a key signaling molecule in the biology of several types of cancer. In this review, we report pieces of evidence regarding the activation of the MEK5-ERK5 pathway as a resistance mechanism to RAF-MEK1/2-ERK1/2 inhibitors. We also highlight the known and possible mechanisms underlying the cross-talks between the ERK1/2 and the ERK5 pathways, the characterization of which is of great importance to maximize, in the future, the impact of RAF-MEK1/2-ERK1/2 targeting. Finally, we emphasize the need of developing additional therapeutically relevant MEK5-ERK5 inhibitors to be used for combined treatments, thus preventing the onset of resistance to cancer therapies relying on RAF-MEK1/2-ERK1/2 inhibitors.

Section 5. Pyrethroid and endosulfan resistance: biology of resistant and susceptible larvae and pupae

1993 ◽  
Vol 1 ◽  
pp. 36-42 ◽  
Author(s):  
Neil W. Forrester ◽  
Matthew Cahill ◽  
Lisa J. Bird ◽  
Jacquelyn K. Layland
Keyword(s):  
Insecticide Resistance ◽  
Larval Development ◽  
Pyrethroid Resistance ◽  
Resistance Management ◽  
Selective Advantage ◽  
Successful Management ◽  
Pupal Development ◽  
Development Times ◽  
Selection Of ◽  
Female Laboratory

SummaryBoth pyrethroid and endosulfan resistant Helicoverpa armigera larvae were shown to have marginally longer development times. Pyrethroid resistant larvae were slower developers often requiring an extra moult before ultimately pupating to the same size pupa as susceptibles. There were no differences between pyrethroid resistant and susceptible pupal development times (male or female). Laboratory and field competition studies could demonstrate no selective advantage for either pyrethroid resistant or susceptible larvae or prepupae. Thus it would seem that the slightly longer larval development times do not manifest as significant biological deficits. This helps explain the gradually deteriorating pyrethroid resistance situation documented during evaluation of the Australian insecticide resistance management (IRM) strategy. There was no evidence of the selection of fitness modifiers (co-adaptation) to overcome the slower development of either pyrethroid or endosulfan resistant larvae. Endosulfan fitness disadvantages were not sufficiently researched in this study to discount the possibility of a fitness deficit contributing to the much more successful management of endosulfan resistance.

Section 4. Pyrethroid and endosulfan resistance: selection and cross resistance studies

1993 ◽  
Vol 1 ◽  
pp. 28-35 ◽  
Author(s):  
Neil W. Forrester ◽  
Matthew Cahill ◽  
Lisa J. Bird ◽  
Jacquelyn K. Layland
Keyword(s):  
Insecticide Resistance ◽  
Lower Order ◽  
Management Strategy ◽  
Pyrethroid Resistance ◽  
Resistance Management ◽  
Resistance Mechanisms ◽  
Cross Resistance ◽  
Male And Female ◽  
Insecticide Resistance Management ◽  
Resistance Selection

SummaryResistance to endosulfan and pyrethroids in Helicoverpa armigera in Australia was shown to be due to multiple rather than cross resistance. The independence of the endosulfan and pyrethroid resistance mechanisms vindicates the sequential use of these two groups in Stages I and II of the insecticide resistance management strategy, respectively. Within the cyclodienes, greatest resistance occurred to dieldrin with lower order cross resistance to endosulfan and endrin. Male and female moths expressed cyclodiene resistance equally.

scholarly journals Impact of an Intervention to Control Imipenem-Resistant Acinetobacter baumannii and Its Resistance Mechanisms: An 8-Year Survey

2021 ◽  
Vol 11 ◽  
Author(s):  
Lida Chen ◽  
Pinghai Tan ◽  
Jianming Zeng ◽  
Xuegao Yu ◽  
Yimei Cai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acinetobacter Baumannii ◽  
Bacterial Resistance ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Minimal Inhibitory Concentrations ◽  
Resistance Rates ◽  
The Impact

BackgroundThis study aimed to examine the impact of an intervention carried out in 2011 to combat multi-drug resistance and outbreaks of imipenem-resistant Acinetobacter baumannii (IRAB), and to explore its resistance mechanism.MethodsA total of 2572 isolates of A. baumannii, including 1673 IRAB isolates, were collected between 2007 and 2014. An intervention was implemented to control A. baumannii resistance and outbreaks. Antimicrobial susceptibility was tested by calculating minimal inhibitory concentrations (MICs), and outbreaks were typed using pulsed-field gel electrophoresis (PFGE). Resistance mechanisms were explored by polymerase chain reaction (PCR) and whole genome sequencing (WGS).ResultsFollowing the intervention in 2011, the resistance rates of A. baumannii to almost all tested antibiotics decreased, from 85.3 to 72.6% for imipenem, 100 to 80.8% for ceftriaxone, and 45.0 to 6.9% for tigecycline. The intervention resulted in a decrease in the number (seven to five), duration (8–3 months), and departments (five to three) affected by outbreaks; no outbreaks occurred in 2011. After the intervention, only blaAMPC (76.47 to 100%) and blaTEM–1 (75.74 to 96.92%) increased (P < 0.0001); whereas blaGES–1 (32.35 to 3.07%), blaPER–1 (21.32 to 1.54%), blaOXA–58 (60.29 to 1.54%), carO (37.50 to 7.69%), and adeB (9.56 to 3.08%) decreased (P < 0.0001). Interestingly, the frequency of class B β-lactamase genes decreased from 91.18% (blaSPM–1) and 61.03% (blaIMP–1) to 0%, while that of class D blaOXA–23 increased to 96.92% (P < 0.0001). WGS showed that the major PFGE types causing outbreaks each year (type 01, 11, 18, 23, 26, and 31) carried the same resistance genes (blaKPC–1, blaADC–25, blaOXA–66, and adeABC), AdeR-S mutations (G186V and A136V), and a partially blocked porin channel CarO. Meanwhile, plasmids harboring blaOXA–23 were found after the intervention.ConclusionThe intervention was highly effective in reducing multi-drug resistance of A. baumannii and IRAB outbreaks in the long term. The resistance mechanisms of IRAB may involve genes encoding β-lactamases, efflux pump overexpression, outer membrane porin blockade, and plasmids; in particular, clonal spread of blaOXA–23 was the major cause of outbreaks. Similar interventions may also help reduce bacterial resistance rates and outbreaks in other hospitals.

scholarly journals Impact of AmpC Derepression on Fitness and Virulence: the Mechanism or the Pathway?

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Marcelo Pérez-Gallego ◽  
Gabriel Torrens ◽  
Jane Castillo-Vera ◽  
Bartolomé Moya ◽  
Laura Zamorano ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Wall ◽  
Antibiotic Resistance ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Major Effect ◽  
Major Step ◽  
Alternative Pathways ◽  
The Impact ◽  
Cell Wall Recycling

ABSTRACTUnderstanding the interplay between antibiotic resistance and bacterial fitness and virulence is essential to guide individual treatments and improve global antibiotic policies. A paradigmatic example of a resistance mechanism is the intrinsic inducible chromosomal β-lactamase AmpC from multiple Gram-negative bacteria, includingPseudomonas aeruginosa, a major nosocomial pathogen. The regulation ofampCexpression is intimately linked to peptidoglycan recycling, and AmpC-mediated β-lactam resistance is frequently mediated by inactivating mutations inampD, encoding anN-acetyl-anhydromuramyl-l-alanine amidase, affecting the levels ofampC-activating muropeptides. Here we dissect the impact of the multiple pathways causing AmpC hyperproduction onP. aeruginosafitness and virulence. Through a detailed analysis, we demonstrate that the lack of all threeP. aeruginosaAmpD amidases causes a dramatic effect in fitness and pathogenicity, severely compromising growth rates, motility, and cytotoxicity; the latter effect is likely achieved by repressing key virulence factors, such as protease LasA, phospholipase C, or type III secretion system components. We also show thatampCoverexpression is required but not sufficient to confer the growth-motility-cytotoxicity impaired phenotype and that alternative pathways leading to similar levels ofampChyperexpression and resistance, such as those involving PBP4, had no fitness-virulence cost. Further analysis indicated that fitness-virulence impairment is caused by overexpressingampCin the absence of cell wall recycling, as reproduced by expressingampCfrom a plasmid in an AmpG (muropeptide permease)-deficient background. Thus, our findings represent a major step in the understanding of β-lactam resistance biology and its interplay with fitness and pathogenesis.IMPORTANCEUnderstanding the impact of antibiotic resistance mechanisms on bacterial pathogenesis is critical to curb the spread of antibiotic resistance. A particularly noteworthy antibiotic resistance mechanism is the β-lactamase AmpC, produced byPseudomonas aeruginosa, a major pathogen causing hospital-acquired infections. The regulation of AmpC is linked to the cell wall recycling pathways, and frequently, resistance to β-lactams is caused by mutation of several of the components of the cell wall recycling pathways such as AmpD. Here we dissect the impact of the pathways for AmpC hyperproduction on virulence, showing that the lack of all threeP. aeruginosaAmpD amidases causes a major effect in fitness and pathogenicity, compromising growth, motility, and cytotoxicity. Further analysis indicated that fitness-virulence impairment is specifically caused by the hyperproduction of AmpC in the absence of cell wall recycling. Our work provides valuable information for delineating future strategies for combatingP. aeruginosainfections by simultaneously targeting virulence and antibiotic resistance.

Aerobic Metabolism Alterations as an Evidence of Underlying Deltamethrin Resistance Mechanisms in Triatoma infestans (Hemiptera: Reduviidae)

2020 ◽  
Vol 57 (6) ◽  
pp. 1988-1991
Author(s):  
Carmen Rolandi ◽  
Gonzalo Roca-Acevedo ◽  
Pablo E Schilman ◽  
Mónica D Germano
Keyword(s):  
Resistance Mechanism ◽  
Resistance Management ◽  
Resistance Mechanisms ◽  
Target Site ◽  
Triatoma Infestans ◽  
Co2 Production ◽  
Mechanisms Of Resistance ◽  
Metabolic Resistance ◽  
Open Flow ◽  
Deltamethrin Resistance

Abstract Triatoma infestans (Klug, 1834), the main vector of Chagas disease in Latin America, is regularly controlled by spraying the pyrethroid deltamethrin, to which some populations have developed resistance. The three main mechanisms of resistance are 1) metabolic resistance by overexpression or increased activity of detoxifying enzymes, 2) target site mutations, and 3) cuticle thickening/modification. We use open-flow respirometry to measure real-time H2O loss rate (V˙H2O) and CO2 production rate (V˙CO2), on nymphs from susceptible and resistant populations before and after exposure to the insecticide to understand the underlying mechanisms of resistance in live insects. Lack of differences in V˙H2O between populations suggested that cuticular thickness/composition is not acting as a relevant resistance mechanism. Similarly, there was no difference in resting V˙CO2, suggesting a trade-off between resistance mechanisms and other physiological processes. The increment in V˙CO2 after application of deltamethrin was similar in both populations, which suggested that while enhanced enzymatic detoxification may play a role in resistance expression in this population, the main mechanism involved should be a passive one such as target site mutations. Open-flow respirometry provided useful evidence for evaluating the mechanisms involved in deltamethrin resistance. Using this technique could improve efficiency of scientific research in the area of insecticide resistance management, leading to a faster decision making and hence improved control results.

scholarly journals Insecticide exposure impacts vector–parasite interactions in insecticide-resistant malaria vectors

2014 ◽  
Vol 281 (1786) ◽  
pp. 20140389 ◽  
Author(s):  
Haoues Alout ◽  
Innocent Djègbè ◽  
Fabrice Chandre ◽  
Luc Salako Djogbénou ◽  
Roch Kounbobr Dabiré ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Competence ◽  
Resistance Mechanisms ◽  
Malaria Vectors ◽  
Anopheles Gambiae S.S ◽  
Strong Trend ◽  
Insecticide Exposure ◽  
The Impact ◽  
Selection Of ◽  
Selection Of Resistance

Currently, there is a strong trend towards increasing insecticide-based vector control coverage in malaria endemic countries. The ecological consequence of insecticide applications has been mainly studied regarding the selection of resistance mechanisms; however, little is known about their impact on vector competence in mosquitoes responsible for malaria transmission. As they have limited toxicity to mosquitoes owing to the selection of resistance mechanisms, insecticides may also interact with pathogens developing in mosquitoes. In this study, we explored the impact of insecticide exposure on Plasmodium falciparum development in insecticide-resistant colonies of Anopheles gambiae s.s. , homozygous for the ace-1 G119S mutation (Acerkis) or the kdr L1014F mutation (Kdrkis). Exposure to bendiocarb insecticide reduced the prevalence and intensity of P. falciparum oocysts developing in the infected midgut of the Acerkis strain, whereas exposure to dichlorodiphenyltrichloroethane reduced only the prevalence of P. falciparum infection in the Kdrkis strain. Thus, insecticide resistance leads to a selective pressure of insecticides on Plasmodium parasites, providing, to our knowledge, the first evidence of genotype by environment interactions on vector competence in a natural Anopheles–Plasmodium combination . Insecticide applications would affect the transmission of malaria in spite of resistance and would reduce to some degree the impact of insecticide resistance on malaria control interventions.

scholarly journals Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Leon M. J. Mugenzi ◽  
Benjamin D. Menze ◽  
Magellan Tchouakui ◽  
Murielle J. Wondji ◽  
Helen Irving ◽  
...  
Keyword(s):  
Pyrethroid Resistance ◽  
Resistance Management ◽  
Anopheles Funestus ◽  
Central Africa ◽  
Malaria Vectors ◽  
Insecticide Treated Nets ◽  
Metabolic Resistance ◽  
P450 Gene ◽  
Regulatory Variants ◽  
The Impact

Abstract Elucidating the genetic basis of metabolic resistance to insecticides in malaria vectors is crucial to prolonging the effectiveness of insecticide-based control tools including long lasting insecticidal nets (LLINs). Here, we show that cis-regulatory variants of the cytochrome P450 gene, CYP6P9b, are associated with pyrethroid resistance in the African malaria vector Anopheles funestus. A DNA-based assay is designed to track this resistance that occurs near fixation in southern Africa but not in West/Central Africa. Applying this assay we demonstrate, using semi-field experimental huts, that CYP6P9b-mediated resistance associates with reduced effectiveness of LLINs. Furthermore, we establish that CYP6P9b combines with another P450, CYP6P9a, to additively exacerbate the reduced efficacy of insecticide-treated nets. Double homozygote resistant mosquitoes (RR/RR) significantly survive exposure to insecticide-treated nets and successfully blood feed more than other genotypes. This study provides tools to track and assess the impact of multi-gene driven metabolic resistance to pyrethroids, helping improve resistance management.

scholarly journals Absence of knockdown mutations in pyrethroid and DDT resistant populations of the main malaria vectors in Colombia

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Lorena I. Orjuela ◽  
Diego A. Álvarez-Diaz ◽  
Juliana A. Morales ◽  
Nelson Grisales ◽  
Martha L. Ahumada ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Pyrethroid Resistance ◽  
Resistance Mechanism ◽  
Point Mutations ◽  
Resistance Mechanisms ◽  
Malaria Vectors ◽  
Anopheles Darlingi ◽  
Metabolic Resistance ◽  
Pyrethroid Insecticides ◽  
Voltage Gated Sodium Channels

Abstract Background Knockdown resistance (kdr) is a well-characterized target-site insecticide resistance mechanism that is associated with DDT and pyrethroid resistance. Even though insecticide resistance to pyrethroids and DDT have been reported in Anopheles albimanus, Anopheles benarrochi sensu lato (s.l.), Anopheles darlingi, Anopheles nuneztovari s.l., and Anopheles pseudopunctipennis s.l. malaria vectors in Latin America, there is a knowledge gap on the role that kdr resistance mechanisms play in this resistance. The aim of this study was to establish the role that kdr mechanisms play in pyrethroid and DDT resistance in the main malaria vectors in Colombia, in addition to previously reported metabolic resistance mechanisms, such as mixed function oxidases (MFO) and nonspecific esterases (NSE) enzyme families. Methods Surviving (n = 62) and dead (n = 67) An. nuneztovari s.l., An. darlingi and An. albimanus mosquitoes exposed to diagnostic concentrations of DDT and pyrethroid insecticides were used to amplify and sequence a ~ 225 bp fragment of the voltage-gated sodium channels (VGSC) gene. This fragment spanning codons 1010, 1013 and 1014 at the S6 segment of domain II to identify point mutations, which have been associated with insecticide resistance in different species of Anopheles malaria vectors. Results No kdr mutations were detected in the coding sequence of this fragment in 129 samples, 62 surviving mosquitoes and 67 dead mosquitoes, of An. darlingi, An. nuneztovari s.l. and An. albimanus. Conclusion Mutations in the VGSC gene, most frequently reported in other species of the genus Anopheles resistant to pyrethroid and DDT, are not associated with the low-intensity resistance detected to these insecticides in some populations of the main malaria vectors in Colombia. These results suggest that metabolic resistance mechanisms previously reported in these populations might be responsible for the resistance observed.

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