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At least 235 records · Page 13Linked to original sources
PubMed2006

Amplification of DNA from preserved specimens shows blowflies were preadapted for the rapid evolution of insecticide resistance.

Mutations of esterase 3 confer two forms of organophosphate resistance on contemporary Australasian Lucilia cuprina. One form, called diazinon resistance, is slightly more effective against commonly used insecticides and is now more prevalent than the other form, called malathion resistance. We report here that the single amino acid replacement associated with diazinon resistance and two replacements associated with malathion resistance also occur in esterase 3 in the sibling species Lucilia sericata, suggesting convergent evolution around a finite set of resistance options. We also find parallels between the species in the geographic distributions of the polymorphisms: In both cases, the diazinon-resistance change is absent or rare outside Australasia where insecticide pressure is lower, whereas the changes associated with malathion resistance are widespread. Furthermore, PCR analysis of pinned specimens of Australasian L. cuprina collected before the release of organophosphate insecticides reveals no cases of the diazinon-resistance change but several cases of those associated with malathion resistance. Thus, the early outbreak of resistance in this species can be explained by the preexistence of mutant alleles encoding malathion resistance. The pinned specimen analysis also shows much higher genetic diversity at the locus before organophosphate use, suggesting that the subsequent sweep of diazinon resistance in Australasia has compromised the scope for the locus to respond further to the ongoing challenge of the insecticides.

Adaptation, Physiological↗
PubMed2006

Changes in viral loads of lamivudine-resistant mutants and evolution of HBV sequences during adefovir dipivoxil therapy.

The addition of adefovir dipivoxil (ADV) to ongoing lamivudine therapy is effective against lamivudine-resistant virus in patients with hepatitis B virus (HBV) infection. We studied 39 patients who received ADV added to lamivudine for breakthrough hepatitis. We determined early viral changes (12 weeks) in YMDD mutants (rtM204I [YIDD sequence], rtM204V [YVDD]) and rtL180M in all 39 patients as well as amino acid changes in the polymerase reverse transcriptase (rt) region and precore/core promoter mutations in 15 patients who received long-term treatment (more than 1 year). Changes in rtM204I and rtL180M viral loads were greater than that of the rtM204V, albeit statistically insignificant. Moreover, the greatest change in viral load was seen for rtM204I without hepatitis B e antigen (HBeAg). The precore mutant was replaced with wild-type virus in three of eight patients after 1 year of added ADV therapy. Compared to baseline with lamivudine therapy only, new amino acid mutations were seen in the rt region at baseline with ADV in seven patients. At 1 year after ADV coadministration, the YMDD motif was replaced with wild-type (rt204M) in two patients, in whom mutations were fewer and of a different type. We conclude that the rtM204I may be more sensitive to ADV in vivo. ADV tended to select wild-type virus from precore mutants. Moreover, viruses that were wild-type in the rt region reappeared after 1 year of ADV coadministration in some patients.

Adenine↗
PubMed1987

A genetic model describing the evolution of levamisole resistance in Trichostrongylus colubriformis, a nematode parasite of sheep.

Data from 21 generations of selection on a levamisole-resistant strain of Trichostrongylus colubriformis, either exposed to selection with the anthelmintics levamisole (LEV) or thiabendazole (TBZ), or unexposed, were used to fit a genetic model describing the evolution of LEV resistance in this parasite species. A statistical model describing the dose-response relationship for a mixed population of susceptible and resistant parasite eggs exposed to anthelmintic was fitted to egg-hatch assay data for each generation and for each selection regimen. Estimated parameters from the statistical model provided the input for the genetic model from which were obtained estimates of the relative fitness of susceptible and resistant genotypes under each selection regimen. The experimental data and the genetic models both indicated that, in this parasite strain, LEV resistance was determined by a single dominant gene, and that TBZ selects for LEV susceptibility. A variety of drug alternation programmes was simulated for this genetic system. The programme that minimized the development of LEV resistance involved alternating the drugs (LEV and TBZ) between each worm generation.

Animals↗
PubMed1998

Evolution of bacterial resistance to antibiotics during the last three decades.

Bacterial resistance to antibiotics is often plasmid-mediated and the associated genes encoded by transposable elements. These elements play a central role in evolution by providing mechanisms for the generation of diversity and, in conjunction with DNA transfer systems, for the dissemination of resistances to other bacteria. At the University Hospital of Zaragoza, extensive efforts have been made to define both the dissemination and evolution of antibiotic resistance by studying the transferable R plasmids and transposable elements. Here we describe the research on bacterial resistance to antibiotics in which many authors listed in the references have participated. The aspects of bacterial resistance dealt with are: (i) transferable resistance mediated by R plasmids in Gram-negative bacteria, (ii) R plasmid-mediated resistance to apramycin and hygromycin in clinical strains, (iii) the transposon Tn1696 and the integron In4, (iv) expression of Escherichia coli resistance genes in Haemophilus influenzae, (v) aminoglycoside-modifying-enzymes in the genus Mycobacterium with no relation to resistance, and (vi) macrolide-resistance and new mechanisms developed by Gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed2003

[Evolution of bacterial resistance to antibiotics].

Bacterial resistance to antibiotics is often plasmid-mediated and the associated genes encoded by transposable elements. These elements play a central role in evolution by providing mechanisms for the generation of diversity and, in conjuntion with DNA transfer systems, for the dissemination of resistance to other bacteria. Resistance to antibiotics in gram-negative bacilli is most commonly mediated by R plasmids and by genes carried by transposons and integrons. In gram-positive cocci the conjugative transposons are fundamental for antibiotic resistance. Acquired multiple R in S. pneumoniae can result from the presence of transposon Tn1545, which carries determinants erm (B), tet (M), aph(3')-III, and catpC194.

Drug Resistance, Bacterial↗
PubMed1980

Phenotypic evolution of cells resistant to bromodeoxyuridine.

Variants resistant to bromodeoxyuridine (BrdUrd) and deficient in thymidine kinase (ATP:thymidine 5'-phosphotransferase; EC 2.7.1.21) have been obtained from V79 Chinese hamster cells by a combination of spontaneous and drug-induced change. Initial mutations take place in wild-type populations as a facilitating step to give partially resistant clones that can be isolated by one-step selection in BrdUrd. When these tolerant populations are maintained for extended periods in BrdUrd-containing medium, a gradual phenotypic transition occurs in which BrdUrd appears to act as an inductive as well as selective agent. Thymidine kinase activity declines logarithmically over an interval of 8-10 weeks as the growth rate rises and the cells become completely resistant to BrdUrd. Relative plating efficiency in hypoxanthine/aminopterin/thymidine medium also decreases, but the decrease is not coordinate with shifts in thymidine kinase activity. The potential for colony formation in hypoxanthine/aminopterin/thymidine continues to decrease exponentially for at least 18 weeks after thymidine kinase deficiency and complete resistance to BrdUrd have been established. These phenotypic modifications are continuous or multistep in character; by clonal analysis they are found to occur in most, if not all, cells maintained in the presence of BrdUrd. Populations in transition thus come to be complex mosaics of different phenotypes that are comparatively stable if isolated in drug-free medium. The progressive evolution of cells resistant to BrdUrd will require new models for an underlying explanation.

Animals↗
PubMed2003

Multidrug efflux pumps and resistance: regulation and evolution.

Multidrug transporters have long puzzled researchers because of their ability to extrude multiple structurally dissimilar toxic chemotherapeutic agents. They appear to be essentially ubiquitous with many microorganisms possessing large arsenals of predicted multidrug efflux transporters. Recent reports on the structures of multidrug efflux transporters and their cognate regulators have suggested that the basis of multidrug recognition is the presence of large flexible hydrophobic cavities capable of accommodating different compounds that are bound via hydrogen bonding and/or electrostatic interactions. This structural data provides the context for understanding other questions about the evolution of multidrug transporters and their natural physiological roles.

Drug Resistance, Multiple↗
PubMed2001

Protease inhibitors and directed evolution: enhancing plant resistance to nematodes.

Plant nematodes are agricultural pests, the control of which relies on chemical nematicides and fumigants that are among the most toxic and environmentally damaging of all agrochemicals. New approaches to control, based on transgenic resistance, would provide important health and environmental benefits. In this chapter we consider briefly some targets for engineering nematode resistance and discuss the use of plant protease inhibitors as anti-feedants. This approach has provided plants that display good levels of resistance against a range of nematode species. To enhance this defence strategy further we are investigating the value of directed evolution to improve the characteristics of protease inhibitors. We describe the approaches of DNA shuffling and phage display that are being used to create and screen variant libraries in the search for inhibitors with improved features.

Animals↗
PubMed2001

Resistance gene complexes: evolution and utilization.

More than 30 genes have been characterized from different plant species that provide resistance to a variety of different pathogen and pest species. The structures of most are consistent with a role in pathogen recognition and defense response signaling. Resistance genes are very abundant in plant genomes and most belong to tightly linked gene families. Evolution of R genes is driven by selection on allelic variation created by mutation and re-assorted by recombination between alleles and sometimes between different gene family members. Selection favors genes that can recognize pathogen avr gene products that are present in pathogen populations. Selection at linked gene families favors haplotypes with useful combinations of genes but a limited physiological cost to the plant. Future utilization of R genes will include transfer between related genera and identification or construction of genes that condition durable resistance to variable pathogens. Genes with durable resistance may interact with conserved pathogen elicitors or condition resistance responses that are independent of specific Avr gene interactions.

Evolution, Molecular↗
PubMed2004

Adaptation to the deleterious effects of antimicrobial drug resistance mutations by compensatory evolution.

Compensatory mutations, due to their ability to mask the deleterious effects of another mutation, are important for the adaptation and evolution of most organisms. Resistance to antibiotics, antivirals, antifungals, herbicides and insecticides is usually associated with a fitness cost. As a result of compensatory evolution, the initial fitness costs conferred by resistance mutations (or other deleterious mutations) can often be rapidly and efficiently reduced. Such compensatory evolution is potentially of importance for (i) the long-term persistence of drug resistance, (ii) reducing the rate of fitness loss associated with the accumulation of deleterious mutations in small asexual populations, and (iii) the evolution of complexity of cellular processes.

Amino Acid Sequence↗
PubMed2006

Adaptive evolution of tetrodotoxin resistance in animals.

Tetrodotoxin (TTX), first isolated from pufferfish (tetraodontids), is a highly potent neurotoxin that selectively binds to voltage-gated sodium channels (Na(v)) in muscle and nerve tissues causing paralysis and death. Saxitoxin (STX) is a TTX-related neurotoxin produced by dinoflagellates. Recent investigations have implicated diverse substitutions in the P-loop regions of skeletal muscle and neuronal Na(v) channels in the convergent evolution of neurotoxin resistance in pufferfish, garter snakes and softshell clams, which has enabled them to feed on TTX- and STX-bearing organisms.

Amino Acid Sequence↗
PubMed1999

Interruption of chemical mosquito control and evolution of insecticide resistance genes in Culex pipiens (Diptera: Culicidae).

Within the Llobregat Delta (Barcelona, Spain), Culex pipiens L. has been the target of organophosphate insecticide (OP) control for 10 yr (1982-1992). Between 1991 and 1992, OPs were replaced by Bacillus-based toxins in all the mosquito control programs within > 150 km of this area. The distribution of several OP-resistance genes was surveyed within the Llobregat Delta and neighboring populations (< 25 km) during the 2 yr following this regional pesticide change to investigate how the change in selection pressure affected the dynamics of OP-resistance genes. The immigration failure of the A2-B2 resistant esterases and the observed difference in OP-resistance dynamics between isolated and nonisolated populations may indicate fitness disadvantages associated with OP-resistance genes, hence a tendency for a decrease in OP-resistance. In contrast, one OP-resistance gene further increased in frequency, whereas the frequencies of some others were maintained. These unexpected results question the importance of pesticides from sources other than mosquito control, and the variability of pleiotropic fitness costs among pesticide resistance genes.

Animals↗
PubMed1994

Evolution of antibiotic resistance: several different amino acid substitutions in an active site loop alter the substrate profile of beta-lactamase.

In order to understand how TEM-1 beta-lactamase substrate specificity can be altered by mutation, amino acid residues 161 through to 170 were randomly mutagenized to sample all possible amino acid substitutions. The 161-170 region includes a portion of an omega loop structure, which is involved in the formation of the active-site pocket. The percentage of random sequences that provide bacterial resistance to either ampicillin or to the extended-spectrum cephalosporin ceftazidime was determined. It was found that the sequence requirements for wild-type levels of ampicillin resistance are much more stringent than the sequence requirements for ceftazidime resistance. Surprisingly, more than 50% of all amino acid substitutions in the 161-170 region result in levels of ceftazidime resistance at least three times greater than wild type. In addition, by increasing the level of the selection for ceftazidime resistance, substitutions that result in a greater than 100-fold increase in ceftazidime resistance were identified. Characterization of altered beta-lactamase enzymes indicated that while their catalytic efficiency (kcat/Km) for ceftazidime hydrolysis is higher, the enzymes are poorly expressed relative to wild-type TEM-1 beta-lactamase.

Amino Acid Sequence↗
PubMed2001

The basic depression ratio of the host: the evolution of host resistance to microparasites.

The basic reproduction ratio R0 occupies a central position in the theory of host pathogen interactions. However, this quantity stresses the role of the pathogen. This paper proposes an additional, more host-centred char acterization using the basic depression ratio D0. This quantity is the number of host individuals per infected by which the infected host population is depressed below its uninfected level. This paper shows that a baseline criterion for the evolution of host resistance to microparasites is that resistance evolves to minimize D0. This parallels the result for pathogen virulence where R0 is maximized. The tension between these two criteria is noted. The framework established allows a discussion of trade-offs between aspects of the pathogen-free host biology and the host pathogen interaction. For certain linear and convex trade-offs it is shown that the strain with the lowest transmission parameter beta wins (despite the fact that it has the lowest intrinsic birth rate a). For corresponding concave trade-offs, either the strain with minimum beta and a or the strain with maximum beta and a wins. Finally the connection with the techniques of adaptive dynamics is made. Evolutionary singular points are shown to occur at extrema of D0. The evolutionary attainment of the results is discussed.

Adaptation, Physiological↗
PubMed1990

Population dynamics of Trichostrongylus colubriformis in sheep: computer model to simulate grazing systems and the evolution of anthelmintic resistance.

A computer model was developed to simulate Trichostrongylus colubriformis populations, their level of resistance to the common anthelmintics, host mortalities and acquired immunity. Predictions were based on sheep management practices such as lambing, weaning, sheep/paddock rotation, anthelmintic treatment, the use of controlled release devices (capsules) for anthelmintic delivery and daily meteorological records to determine the development and survival of infective larvae (L3) on pasture. Evolution of drug resistance was determined by a simple genetic system which allowed for up to three genes, each with two alleles, to give a maximum of 27 genotypes associated with one drug or three genotypes for each of three drugs. The model was validated against egg counts, L3 counts on pasture and host mortalities observed in a grazing trial, however, aspects of the model such as the development of drug resistance and use of the model in a variety of climatic zones have yet to be tested against field observations. The model was used to examine the impact of grazing management and capsule use on anthelmintic resistance and sheep production over 20 years using historical weather data. Predictions indicated that grazing management can play a dominant role in parasite control and that capsule use will reduce sheep mortalities and production losses, and in some circumstances will not cause a substantial increase in anthelmintic resistance for up to 5 years.

Animals↗