scholarly journals Oxydemeton-Methyl Resistance, Mechanisms, and Associated Fitness Cost in Green Peach Aphids (Hemiptera: Aphididae)

2008 ◽  
Vol 101 (4) ◽  
pp. 1432-1438 ◽  
Author(s):  
M. Ghadamyari ◽  
K. Talebi ◽  
H. Mizuno ◽  
Y. Kono
Keyword(s):  
Resistance Mechanisms ◽  
Fitness Cost ◽  
Green Peach Aphids

scholarly journals Differential Resistance Mechanisms to Glyphosate Result in Fitness Cost for Lolium perenne and L. multiflorum

2017 ◽  
Vol 8 ◽  
Author(s):  
Pablo T. Fernández-Moreno ◽  
Ricardo Alcántara-de la Cruz ◽  
Reid J. Smeda ◽  
Rafael De Prado
Keyword(s):  
Lolium Perenne ◽  
Differential Resistance ◽  
Resistance Mechanisms ◽  
Fitness Cost

scholarly journals Development of in Vitro Resistance to Daptomycin in Enterococcus Faecium and Estimation of Its Fitness Cost

2020 ◽  
Author(s):  
Weiliang Zeng ◽  
Tao Chen ◽  
Qing Wu ◽  
Ye Xu ◽  
Kaihang Yu ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Resistance Mechanisms ◽  
Fitness Cost ◽  
Resistant Bacteria ◽  
Infection Model ◽  
Dynamic Resistance ◽  
Vancomycin Resistant

Abstract BackgroundDaptomycin has broad-spectrum antibacterial activity against Gram-positive pathogens, but recent studies have revealed cases where daptomycin has failed to treat multidrug-resistant bacteria, such as vancomycin-resistant Enterococcus faecium. However, the resistance evolution of E. faecium to daptomycin in vitro and fitness cost remain unclear. In this study, we sought to analyze the resistance development and mechanism of E. faecium to datomycin, and futher to investigate the relationship between daptomycin resistance and fitness cost.MethodsTo investigate the development of daptomycin resistance in E. faecium, 6 daptomycin-susceptible (DAP-S) clinical isolates, including 3 vancomycin-resistant E. faecium (VRE) and 3 vancomycin-susceptible E. faecium (VSE), were exposured to daptomycin in vitro by serial passage experiment. Then the different resistance mechanisms of daptomycin-resistant (DAP-R) mutants were analyzed by polymerase chain reaction (PCR), cytochrome C binding assay and transmission electron microscopy. Furthermore, we also estimated the changes of fitness cost among each highly DAP-R mutants by bacterial growth curve measurement, in vitro competition experiments, infection model of Galleria mellonella larvae and biofilm formation assays.ResultsIn vitro, a total of 21 DAP-R mutants with minimal inhibitory concentration (MIC) of 4 to 512 μg/mL were obtained, and these mutants carried more than one mutation of LiaFSR and YycFG system encoding genes. More positive charges were detected among highly DAP-R mutants than parent isolates, and the cell walls of SC1174-D and SC1762-D mutants were remarkly thicker than those of the parent isolates. In comparison with parent isolates, besides, the growth, competition ability and virulence were significantly reduced, while the biofilm formation capacity was markedly elevated among each highly DAP-R mutants.ConclusionsOur findings suggest that E. faecium isolates are able to rapidly acquire DAP resistance in vitro through different dynamic resistance mechanisms, which often accompany by significant fitness cost. Intriguingly, DAP and glycopeptide antibiotics may present collateral-sensitivity during E. faecium acquired DAP resistance in vitro.

Mechanisms and phenotypic consequences of acquisition of tigecycline resistance by Stenotrophomonas maltophilia

2019 ◽  
Vol 74 (11) ◽  
pp. 3221-3230 ◽  
Author(s):  
Paula Blanco ◽  
Fernando Corona ◽  
José Luis Martinez
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Efflux Pump ◽  
Maximum Growth ◽  
Opportunistic Pathogen ◽  
Resistance Mechanisms ◽  
Fitness Cost ◽  
Negative Regulator ◽  
Cross Resistance ◽  
Bacterial Fitness ◽  
High Level

Abstract Objectives To elucidate the potential mutation-driven mechanisms involved in the acquisition of tigecycline resistance by the opportunistic pathogen Stenotrophomonas maltophilia. The mutational trajectories and their effects on bacterial fitness, as well as cross-resistance and/or collateral susceptibility to other antibiotics, were also addressed. Methods S. maltophilia populations were submitted to experimental evolution in the presence of increasing concentrations of tigecycline for 30 days. The genetic mechanisms involved in the acquisition of tigecycline resistance were determined by WGS. Resistance was evaluated by performing MIC assays. Fitness of the evolved populations and individual clones was assessed by measurement of the maximum growth rates. Results All the tigecycline-evolved populations attained high-level resistance to tigecycline following different mutational trajectories, yet with some common elements. Among the mechanisms involved in low susceptibility to tigecycline, mutations in the SmeDEF efflux pump negative regulator smeT, changes in proteins involved in the biogenesis of the ribosome and modifications in the LPS biosynthesis pathway seem to play a major role. Besides tigecycline resistance, the evolved populations presented cross-resistance to other antibiotics, such as aztreonam and quinolones, and they were hypersusceptible to fosfomycin, suggesting a possible combination treatment. Further, we found that the selected resistance mechanisms impose a relevant fitness cost when bacteria grow in the absence of antibiotic. Conclusions Mutational resistance to tigecycline was easily selected during exposure to this antibiotic. However, the fitness cost may compromise the maintenance of S. maltophilia tigecycline-resistant populations in the absence of antibiotic.

scholarly journals Evolution of resistance mechanisms and biological characteristics of rifampicin-resistant Staphylococcus aureus strains selected in vitro

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chong Wang ◽  
Renchi Fang ◽  
Beibei Zhou ◽  
Xuebin Tian ◽  
Xiucai Zhang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Galleria Mellonella ◽  
Resistance Mechanisms ◽  
Fitness Cost ◽  
Rifampicin Resistance ◽  
Infection Model ◽  
Resistance Mutations ◽  
Evolution Of Resistance ◽  
The Impact

Abstract Background We aimed to determine the evolutionary pathways of rifampicin resistance in Staphylococcus aureus, and the impact of resistance mutations in the rpoB gene on fitness. Methods Three clinical strains and one reference strain were used to select for rifampicin-resistant S. aureus variants. The mutations responsible for rifampicin resistance in all of the selected isolates in vitro were investigated by polymerase chain reaction (PCR) and DNA sequencing. To compare the fitness cost of rpoB mutations against their corresponding original isolates, we performed bacterial growth curve assays, static biofilm assays, in vitro competition experiments and an infection model of Galleria mellonella larvae. Results We obtained four rifampicin-resistant S. aureus isolates that showed high levels of resistance to rifampicin with a minimal inhibitory concentration (MIC) of 128 mg/L, and all isolates had a mutation at position 481 (H481F/Y) in RpoB. A broth microdilution assay indicated that mutation of H481F/Y did not affect susceptibility to common antibacterial drugs but slightly increased the vancomycin MIC. To identify the pathways involved in the development of rifampicin resistance, 32 variants (eight mutants for each strain) and four original isolates were selected for gene sequencing. Different generations of isolates were found to harbor various mutations sites. Compared with the corresponding original isolates, an in vitro fitness assay of the variant isolates showed that growth and virulence were reduced, with a statistically significantly decreased fitness, whereas the capacity for biofilm formation was elevated. Conclusions Our findings suggested that the acquisition of rifampicin resistance in S. aureus was dynamic and was associated with a significant fitness cost.

scholarly journals Fitness costs of individual and combined pyrethroid resistance mechanisms, kdr and CYP-mediated detoxification, in Aedes aegypti

2021 ◽  
Vol 15 (3) ◽  
pp. e0009271
Author(s):  
Letícia B. Smith ◽  
Juan J. Silva ◽  
Connie Chen ◽  
Laura C. Harrington ◽  
Jeffrey G. Scott
Keyword(s):  
Aedes Aegypti ◽  
Pyrethroid Resistance ◽  
Resistance Mechanisms ◽  
Fitness Cost ◽  
Adult Longevity ◽  
Cost Ratio ◽  
Resistance Mutations ◽  
Fitness Costs ◽  
Net Reproductive Rate ◽  
Mating Competition

Background Aedes aegypti is an important vector of many human diseases and a serious threat to human health due to its wide geographic distribution and preference for human hosts. A. aegypti also has evolved widespread resistance to pyrethroids due to the extensive use of this insecticide class over the past decades. Mutations that cause insecticide resistance result in fitness costs in the absence of insecticides. The fitness costs of pyrethroid resistance mutations in A. aegypti are still poorly understood despite their implications for arbovirus transmission. Methodology/Principle findings We evaluated fitness based both on allele-competition and by measuring specific fitness components (i.e. life table and mating competition) to determine the costs of the different resistance mechanisms individually and in combination. We used four congenic A. aegypti strains: Rockefeller (ROCK) is susceptible to insecticides; KDR:ROCK (KR) contains only voltage-sensitive sodium channel (Vssc) mutations S989P+V1016G (kdr); CYP:ROCK (CR) contains only CYP-mediated resistance; and CYP+KDR:ROCK (CKR) contains both CYP-mediated resistance and kdr. The kdr allele frequency decreased over nine generations in the allele-competition study regardless of the presence of CYP-mediated resistance. Specific fitness costs were variable by strain and component measured. CR and CKR had a lower net reproductive rate (R0) than ROCK or KR, and KR was not different than ROCK. There was no correlation between the level of permethrin resistance conferred by the different mechanisms and their fitness cost ratio. We also found that CKR males had a reduced mating success relative to ROCK males when attempting to mate with ROCK females. Conclusions/Significance Both kdr and CYP-mediated resistance have a fitness cost affecting different physiological aspects of the mosquito. CYP-mediated resistance negatively affected adult longevity and mating competition, whereas the specific fitness costs of kdr remains elusive. Understanding fitness costs helps us determine whether and how quickly resistance will be lost after pesticide application has ceased.

scholarly journals Investigation of Relative Development and Reproductivity Fitness Cost in Three Insecticide-Resistant Strains of Aedes aegypti from Thailand

Insects ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 265 ◽  
Author(s):  
Jassada Saingamsook ◽  
Jintana Yanola ◽  
Nongkran Lumjuan ◽  
Catherine Walton ◽  
Pradya Somboon
Keyword(s):  
Aedes Aegypti ◽  
Egg Production ◽  
Natural Populations ◽  
Blood Feeding ◽  
Developmental Time ◽  
Resistance Mechanisms ◽  
Fitness Cost ◽  
Detoxification Enzymes ◽  
Relative Fitness ◽  
Resistant Strains

Knockdown resistance (kdr) and detoxification enzymes are major resistance mechanisms in insecticide-resistant Aedes aegypti throughout the world. Persistence of the resistance phenotype is associated with high fitness of resistance alleles in the absence of insecticide pressure. This study determined the relative fitness cost of three insecticide-resistant strains of Aedes aegypti—PMD, PMD-R, and UPK-R—and a hybrid under similar laboratory conditions in the absence of insecticide. The PMD strain is resistant to DDT with no kdr alleles; the PMD-R is resistant to DDT and permethrin with 1534C homozygous kdr alleles; and UPK-R is resistant to DDT, permethrin, and deltamethrin with 989P + 1016G homozygous alleles. The DDT-resistant PMD strain had the highest fitness compared with the two DDT/pyrethroid-resistant strains (PMD-R and UPK-R) and hybrid. Consistent fitness costs were observed in the DDT/pyrethroid-resistant strains and hybrid, including shorter wing length, reduced egg hatchability, shorter female lifespan, and shorter viability of eggs after storage, whereas no effect was observed on blood feeding rate. In addition, reduced egg production was observed in the PMD-R strain and prolonged developmental time was seen in the UPK-R strain. The corresponding hybrid that is heterozygous for kdr alleles was fitter than either of the homozygous mutant genotypes. This is in accordance with the high frequency of heterozygous genotypes observed in natural populations of Ae. aegypti in Chiang Mai city.

Resistance mechanisms ofPrunusrootstocks to root-knot nematode,Meloidogyne incognita

Fruits ◽  
2009 ◽  
Vol 64 (5) ◽  
pp. 295-303 ◽  
Author(s):  
Hang Ye ◽  
Wen-jun Wang ◽  
Guo-jie Liu ◽  
Li-xin Zhu ◽  
Ke-gong Jia
Keyword(s):  
Meloidogyne Incognita ◽  
Resistance Mechanisms ◽  
Root Knot Nematode

Emerging Antimicrobial Resistance Among Methicillin Resistant Staphylococcus Aureus (MRSA) in a Tertiary Care Centre in North India

JMS SKIMS ◽  
2020 ◽  
Vol 23 (1) ◽  
pp. 48-49
Author(s):  
Javaid Ahmad Bhat ◽  
Shariq Rashid Masoodi
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Tertiary Care ◽  
Resistance Mechanisms ◽  
North India ◽  
Global Public Health ◽  
Care Centre ◽  
Tertiary Care Centre ◽  
Effective Prevention ◽  
Mupirocin Resistance

Apropos to the article by Dr Bali, titled “Mupirocin resistance in clinical isolates of methicillin-sensitive and resistant Staphylococcus aureus in a tertiary care centre of North India” (1), the authors have raised important issue of emerging antimicrobial resistance (AMR). Antimicrobial resistance is an increasingly serious threat to global public health that requires action across all government sectors and society. As per WHO, AMR lurks the effective prevention and management of an ever-increasing spectrum of infections caused by bacteria, parasites, fungi and viruses. Novel resistance mechanisms are emerging and spreading globally, threatening the man’s ability to treat common infectious diseases.

Evaluation of Potent Isoquinoline-Based Thiosemicarbazone Antiproliferatives Against Solid Tumor Models

2019 ◽  
Author(s):  
Daniel Sun ◽  
Soumya Poddar ◽  
Roy D. Pan ◽  
Juno Van Valkenburgh ◽  
Ethan Rosser ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Small Cell Lung Carcinoma ◽  
Single Agent ◽  
Resistance Mechanisms ◽  
Tumor Models ◽  
Cell Lung Carcinoma ◽  
Adaptive Resistance ◽  
Cancer Models ◽  
Nanomolar Range

The lead compound, an ⍺-N-heterocyclic carboxaldehyde thiosemicarbazone <b>HCT-13</b>, was highly potent against a panel of pancreatic, small cell lung carcinoma, and prostate cancer models, with IC<sub>90</sub> values in the low-to-mid nanomolar range.<b> </b>We show that the cytotoxicity of <b>HCT-13</b> is copper-dependent, that it acts as a copper ionophore, induces production of reactive oxygen species (ROS), and promotes mitochondrial dysfunction and S-phase arrest. Lastly, DNA damage response/replication stress response (DDR/RSR) pathways, specifically Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (ATR), were identified as actionable adaptive resistance mechanisms following <b>HCT-13 </b>treatment. Taken together, <b>HCT-13 </b>is potent against solid tumor models and warrants <i>in vivo</i> evaluation against aggressive tumor models, either as a single agent or as part of a combination therapy.

5-Benzylidene-4-Oxazolidinones are Synergistic with Antibiotics for the Treatment of Staphylococcus Aureus Biofilms

2019 ◽  
Author(s):  
Bram Frohock ◽  
Jessica M. Gilbertie ◽  
Jennifer C. Daiker ◽  
Lauren V. Schnabel ◽  
Joshua Pierce
Keyword(s):  
Staphylococcus Aureus ◽  
Human Health ◽  
Matrix Model ◽  
Bacterial Load ◽  
Collagen Matrix ◽  
Resistance Mechanisms ◽  
Novel Therapeutics ◽  
Innovative Treatment ◽  
Antibiotic Action ◽  
Biofilm Infection

<div>The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative treatment approaches to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms and in combination with common antibiotics are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.</div>

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