The Central Role of Multiple P450 Genes and Their Co-factor CPR in the Development of Permethrin Resistance in the Mosquito Culex quinquefasciatus

Mosquitoes’ increasing resistance to insecticides is becoming a major threat for control efforts worldwide. Multiple P450 genes that are up-regulated in permethrin resistant strains of Culex quinquefasciatus have been linked to the development of resistance. In the current study, we characterized the function of six P450 genes, CYP6P14, CYP6BZ2, CYP9J33, CYP9J34, CYP9J40, and CYP9J45, that are overexpressed in the permethrin resistant Culex mosquitoes and showed their capability in metabolism of permethrin. These six P450 genes can convert 3-phenoxybenzoic alcohol (PBCHO) to a less toxic product, 3-phenoxybenzoic acid (PBCOOH), indicating that these P450s play an important role in permethrin degradation pathways. Although we know multiple P450 genes are over-expressed in permethrin resistant Culex mosquitoes, it remains to be seen whether cytochrome P450-reductase (CPR) gene that are co-overexpressed with P450 genes in permethrin resistant mosquitoes do indeed serve as a resistance mechanism. An in-depth investigation of the expression of CPR gene in resistant mosquitoes was conducted in permethrin resistant mosquitoes. The finding of CPR gene overexpression in permethrin resistant mosquitoes suggested the importance of co-overexpression of multiple P450 genes with their obligatory electron donor CPR in the complex detoxification system, boosting the metabolism of permethrin and hence the development of permethrin resistance in Cx. quinquefasciatus.

Download Full-text

Evolution of the phenomenon of drug-resistance III. The origin of the development of resistance to sulphathiazole in Escherichia coli and Staphylococcus aureus

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1960.0098 ◽

1960 ◽

Vol 153 (951) ◽

pp. 220-233 ◽

Cited By ~ 4

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Resistance Mechanism ◽

Preceding Paper ◽

Resistant Cell ◽

Cell System ◽

Toxic Agent ◽

Staphylococcal Strain ◽

Resistant Strains

This study deals with the hourly determination of metabolic differences during growth with sulphathiazole (ST) between the ST-sensitive and ST-resistant strains of Escherichia coli and Staphylococcus aureus for the timing of the onset of resistance mechanism. The amounts of the extracellularly accumulated p-aminobenzoic acid (PAB), folic acid (FA) and citrovorum factor (CF) in the culture fluids and the growth rates are determined. As described in the preceding paper, the sequence of metabolic events with these strains is of the same pattern. The PAB curve in the resistant cell system with ST rises perpendicularly to a peak and then declines sharply followed by the rise of the growth curve. In contrast, in the sensitive cell system with ST, the PAB curve, after reaching a peak, forms a longlasting plateau or a dome-like plateau. During these plateau periods growth is absent. The decline in the plateau is followed by growth. In both the sensitive and resistant strains (E. coli ), the extracellularly accumulated PAB are quantitatively alike. Nevertheless, the PAB in the sensitive system is incapable of antagonizing ST which is of from 10- to 20-fold smaller amount than in the resistant system. As the antagonism of PAB to ST takes place the PAB curve declines and growth is initiated. These events are coincidental with the acquisition of resistance to ST during the PAB plateau period. The similar events in the ST-sensitive staphylococcal strain are associated with the development of the satellism .phenomenon. This phenomenon is manifested on the agar plates with ST until resistance is acquired. The resistant staphylococcal strain does not manifest the phenomenon of satellism. The data presented here and elsewhere are extrapolated to formulate the thesis that a drug or toxic agent exercises two roles on a living system: One, the role of a negative catalyst , and two, the role of a positive catalyst . The latter neutralizes the former giving rise to the phenomenon of resistance, or the evolution of biochemical mechanisms by which a living cell survives the action of toxic agents. A toxin of bacterial or other origins functions in a manner similar to the actions of drugs on bacteria giving rise to the immunological defence mechanism.

Download Full-text

The role of nitrogen in transforming British agricultural productivity production prior to and during the First World War

Global Environment ◽

10.3197/ge.2020.130304 ◽

2020 ◽

Vol 13 (3) ◽

pp. 583-609

Author(s):

John Martin

Keyword(s):

Agricultural Production ◽

First World War ◽

World War ◽

Coal Gas ◽

Major Threat ◽

The First World War ◽

Food Shortages ◽

War Effort ◽

First World

This paper explores the reasons why artificial or mineral sources of nitrogen, which were more readily available in Britain than in other European countries, were only slowly adopted by farmers in the decades prior to and during the First World War. It considers why nitrogen in the form of sulphate of ammonia, a by-product of coal-gas (town-gas) manufacture, was increasingly exported from Britain for use by German farmers. At the same time Britain was attempting to monopolise foreign supplies of Chilean nitrate, which was not only a valuable source of fertiliser for agriculture but also an essential ingredient of munitions production. The article also investigates the reasons why sulphate of ammonia was not more widely used to raise agricultural production during the First World War, at a time when food shortages posed a major threat to public morale and commitment to the war effort.

Download Full-text

Role of Artesunate in Potentiation of β-lactam Against Methicillin Resistant Staphylococcus aureus (MRSA) Isolated from Bovine Mastitis and its Histopathology Impact In-Vivo Study

International Journal of Veterinary Science ◽

10.37422/ijvs/030 ◽

2020 ◽

Keyword(s):

Clavulanic Acid ◽

Resistance Mechanism ◽

Bovine Mastitis ◽

Lethal Challenge ◽

Experimental Procedure ◽

Appropriate Treatment ◽

Amoxicillin Clavulanic Acid ◽

Mrsa Infection

This article discusses the augmenting influence of Artesunate (ART) in combination with β-lactams (amoxicillin/clavulanic acid) antibiotic in sepsis mice models infected by a lethal challenge dose of live coagulase positive enterotoxigenic (Sec) MRSA that was isolated from a case of chronic bovine mastitis. The main goal is to find an appropriate treatment to overcome resistance mechanism of MRSA towards β-lactams antibiotic. Fifty healthy adult Swiss mice divided into 5 equal groups were used in the experimental procedure. The infected group that treated with both ART and β-lactams (amoxicillin/clavulanic acid) antibiotic revealed complete inhibition of MRSA count with complete normal macroscopic and histopathological features. We suggest that ART can potentiate the antibacterial action of β-lactams (amoxicillin/Clavulanic) acid against MRSA infection. The combination of ART and antibiotic can overcome MRSA resistance mechanism and so could be considered a novel candidate to overcome mastitis and/or sepsis caused by MRSA.

Download Full-text

Probing the role of lysines and arginines in the catalytic function of cytochrome P450d by site-directed mutagenesis. Interaction with NADPH-cytochrome P450 reductase

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)67801-4 ◽

1991 ◽

Vol 266 (6) ◽

pp. 3372-3375

Author(s):

T Shimizu ◽

T Tateishi ◽

M Hatano ◽

Y Fujii-Kuriyama

Keyword(s):

Cytochrome P450 ◽

Site Directed Mutagenesis ◽

Directed Mutagenesis ◽

Cytochrome P450 Reductase ◽

Nadph Cytochrome ◽

P450 Reductase ◽

Catalytic Function ◽

Nadph Cytochrome P450 Reductase

Download Full-text

Role of protein S-Glutathionylation in cancer progression and development of resistance to anti-cancer drugs

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2021.108890 ◽

2021 ◽

Vol 704 ◽

pp. 108890

Author(s):

Debojyoti Pal ◽

Archita Rai ◽

Rahul Checker ◽

R.S. Patwardhan ◽

Babita Singh ◽

...

Keyword(s):

Cancer Progression ◽

Protein S ◽

Cancer Drugs ◽

Development Of Resistance ◽

Anti Cancer

Download Full-text

Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen Pyricularia oryzae

International Journal of Molecular Sciences ◽

10.3390/ijms22073731 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3731

Author(s):

Andrea Kunova ◽

Luca Palazzolo ◽

Fabio Forlani ◽

Giorgia Catinella ◽

Loana Musso ◽

...

Keyword(s):

Rice Blast ◽

Rational Design ◽

Structural Investigation ◽

Resistance Mechanism ◽

Three Dimensional ◽

Pyricularia Oryzae ◽

Cytochrome Bc1 ◽

Cytochrome Bc1 Complex ◽

Three Dimensional Model ◽

Resistant Strains

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen.

Download Full-text