PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “resistance evolution”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

Modeling the impact of alternative hosts on Helicoverpa zea adaptation to bollgard cotton.

For highly polyphagous cotton, Gossypium hirsutum L., pests such as Helicoverpa zea (Boddie), a substantial portion of the larval population develops on noncotton alternative hosts. These noncotton hosts potentially provide a natural refuge for H. zea, thereby slowing the evolution of resistance to the Bacillus thuringiensis Berliner (Bt)-derived Cry1Ac protein present in Bollgard cotton. Here, we demonstrate how the measured contribution of such alternative hosts can be included in estimating the "effective refuge" present for H. zea and in modeling resistance evolution in this species. A single-gene, two-compartment model was used in which one compartment represented corn, Zea mays L., and cotton that express the Cry1Ac protein or similar proteins, and the other compartment was the effective refuge, made up of a weighted average of non-Bt cotton and noncotton hosts. The effective refuge was estimated for each of six generations of H. zea based upon available data on larval population densities on different hosts and cropping patterns. Model runs were performed for regions centered on three states: Georgia, Mississippi, and North Carolina. Three sets of fitness cost assumptions for the putative resistance gene were used: none, low, and moderate, with either recessive or additive inheritance for resistance and fitness costs. For Georgia and North Carolina, resistance was predicted to take >30 yr to evolve except in the absence of fitness costs. For Mississippi, results were sensitive to fitness costs: >30 yr with moderate costs, 7-14 yr with low costs, and 6-10 yr without such costs.

Animals↗

Molecular biology and evolution of resistance of toxicants.

To the prevailing biochemical/physiological classification of mechanisms of organismal resistance to toxicants, an additional molecular dimension is proposed. Predictions are developed regarding the relative prevalence of different classes of mutations and are found to compare favorably with reports from the literature. In particular, point mutations in target loci were the dominant form of resistance for both lab and field selection. Amplifications of target loci were less common than structural mutations, and more common for lab-selected than for field-selected strains. Amplification was the most common mechanism of up-regulation of metabolizing enzymes. In comparison, only one mutation involving cis-regulation and several involving trans-acting regulation were found. Mutations involving gene disruption and down-regulation were uncommon, but were found in appropriate cases, i.e., when toxicants stimulated rather than inhibited target function and when metabolizing enzymes converted toxicants into more toxic metabolites. Additional phenomena of likely but uncertain importance are genetic "succession," recombinational limitation, and negative cross-resistance. More work on these phenomena and on quantification of fitness costs of resistance is recommended.

Animal Population Groups↗

Evolution of resistance during clonal expansion.

Acquired drug resistance is a major limitation for cancer therapy. Often, one genetic alteration suffices to confer resistance to an otherwise successful therapy. However, little is known about the dynamics of the emergence of resistant tumor cells. In this article, we consider an exponentially growing population starting from one cancer cell that is sensitive to therapy. Sensitive cancer cells can mutate into resistant ones, which have relative fitness alpha prior to therapy. In the special case of no cell death, our model converges to the one investigated by Luria and Delbrück. We calculate the probability of resistance and the mean number of resistant cells once the cancer has reached detection size M. The probability of resistance is an increasing function of the detection size M times the mutation rate u. If Mu << 1, then the expected number of resistant cells in cancers with resistance is independent of the mutation rate u and increases with M in proportion to M(1-1/alpha) for advantageous mutants with relative fitness alpha>1, to l nM for neutral mutants (alpha = 1), but converges to an upper limit for deleterious mutants (alpha<1). Further, the probability of resistance and the average number of resistant cells increase with the number of cell divisions in the history of the tumor. Hence a tumor subject to high rates of apoptosis will show a higher incidence of resistance than expected on its detection size only.

Antineoplastic Agents↗

Experimental evolution of resistance to an antimicrobial peptide.

A novel class of antibiotics based on the antimicrobial properties of immune peptides of multicellular organisms is attracting increasing interest as a major weapon against resistant microbes. It has been claimed that cationic antimicrobial peptides exploit fundamental features of the bacterial cell so that resistance is much less likely to evolve than in the case of conventional antibiotics. Population models of the evolutionary genetics of resistance have cast doubt on this claim. We document the experimental evolution of resistance to a cationic antimicrobial peptide through continued selection in the laboratory. In this selection experiment, 22/24 lineages of Escherichia coli and Pseudomonas fluorescens independently evolved heritable mechanisms of resistance to pexiganan, an analogue of magainin, when propagated in medium supplemented with this antimicrobial peptide for 600-700 generations.

Animals↗

[Evolution as resistance to entropy. I. Mechanisms of species homeostasis].

The idea is discussed that the common output of any evolution is creation of the entities that are increasingly resistant to further evolution. The moving force of evolution is entropy, the tendency to disorder. This general aspiration for chaos is a cause of the mortality of organisms and species, however, being prerequisite for any movement, it creates (by chance) novelties, which may occur (by chance) more resistant to further decay and thus survive. The surviving of those who survive is the most general principle of evolution discovered by Darwin for particular case of biological evolution. The second law of thermodynamics states that our Universe is perishing but its ontology is such that it creates resistance to destruction. The evolution is a history of this resistance. Not only those who die do not survive but also those who evolve. The entities that change (evolve) rapidly disappear rapidly and by this reason they are not observed among both the fossils and now-living organisms. We know only about long-living species. All the existing organisms are endowed with an ability to resist other changing. The following main achievements of the species homeostasis are discussed: high fidelity of DNA replication and effective mechanisms of DNA repair; diploidy; normalizing selection; truncated selection; heterozygote superiority; ability to change phenotype adaptively without changing genotype; parental care and the K-strategy of reproduction; behavior that provides independence of the environment. The global resistance of the living systems to entropy is provided the state that all the essential in biology is determined not by physical-chemical interactions but could semantic rules. A conception of "potential zygotic information" that determines the rules of ontogenesis is proposed. A zygote does not contain this information in explicit form. It is created de novo step by step during ontogenesis and it could not be decoded beforehand. The experimental data on the adaptive mutagenesis and the relevant hypothesis are discussed. It is concluded that the special mechanisms for speeding-up of evolution as created by evolution are impossible conceptually.

Adaptation, Biological↗

Evolution of resistance toward Bacillus sphaericus or a mixture of B. sphaericus+Cyt1A from Bacillus thuringiensis, in the mosquito, Culex quinquefasciatus (Diptera: Culicidae).

The 2362 strain of Bacillus sphaericus (Bs) Neide is a highly mosquitocidal bacterium used in commercial bacterial larvicides primarily to control mosquitoes of the genus Culex. Unfortunately, Bs is at high risk for selecting resistance in mosquito populations, because its binary toxin apparently only binds to a single receptor type on midgut microvilli. A potential key strategy for delaying resistance to insecticidal proteins is to use mixtures of toxins that act at different targets within the insect, especially mixtures that interact synergistically. We tested this hypothesis for delaying the phenotypic expression of resistance by exposing Culex quinquefasciatus Say larvae to Bs alone or in combination with Cyt1A from Bacillus thuringiensis subsp. israelensis. Two laboratory lines of Cx. quinquefasciatus, one sensitive to Bs and the other containing Bs resistance alleles, were subjected to intensive selection pressure for 20 generations with either Bs 2362 or a 3:1 mixture of Bs 2362+Cyt1A. At the end of the study, the sensitive line had evolved >1000-fold resistance when selected with Bs alone, whereas the parallel line selected with Bs+Cyt1A exhibited only low resistance toward this mixture (RR95, 1.4). Similar results were observed in the lines containing Bs resistance alleles. Both lines selected with Bs+Cyt1A exhibited substantial resistance to Bs in the absence of Cyt1A. Although selection with Bs+Cyt1A did not prevent the underlying evolution of resistance to Bs, these results suggest that a mixture of Bs with other endotoxins, particularly one like Bs+Cyt1A in which the components interact synergistically, will provide longer lasting and more effective mosquito control than Bs alone.

Animals↗

Evolution of resistance to metronidazole and clarithromycin in Helicobacter pylori clinical isolates from Spain.

The aim of this study was to determine the frequency of resistance to amoxycillin, tetracycline, metronidazole and clarithromycin in 282 Helicobacter pylori clinical isolates from Spain and to evaluate the evolution of resistance over the five years of this study. The overall percentage of resistance was 19.9% for metronidazole and 3.5% for clarithromycin. Resistance to metronidazole rose from 9% in 1991 to 21.6% in 1995, although 33.3% resistance was found in 1993. Clarithromycin resistance was not detected in 1991 or 1992 and the rate was 4%, 3.4% and 4.4% in 1993, 1994 and 1995, respectively. No amoxycillin or tetracycline resistance was found.

Adolescent↗

Evolution of resistance in the presence of two insecticides.

A two-locus model is used to analyze the effectiveness of a mixture of insecticides in delaying resistance, compared to the use of the insecticides singly. The effects of factors such as recombination, effective dominance, initial value of allele frequencies and initial value of linkage disequilibrium are considered. It is shown that the use of mixtures is always more effective in delaying the onset of resistance, often by many orders of magnitude. It is shown that there exists a threshold value of recombination fraction, above which the evolution of resistance is extremely slow. Resistance evolves very rapidly for values of recombination fraction below the threshold. Finally, the relevance of these results on resistance management is discussed.

Animals↗

Evolution of resistance patterns and identification of risk factors for Streptococcus pneumoniae colonisation in daycare centre attendees in Athens, Greece.

Two cross-sectional surveillance studies were conducted during the winters of 2000 and 2003 in Athens, Greece, to obtain nasopharyngeal swabs from healthy pre-school children attending kindergartens. A total of 460 strains were examined in 2000 and 485 strains in 2003, with carriage rates of 31.7% and 34.6%, respectively. Susceptibility patterns were evaluated for penicillin G, erythromycin, ceftriaxone, moxifloxacin, linezolid and telithromycin. Penicillin non-susceptibility increased from 20% to 34.9%, whereas erythromycin non-susceptibility increased from 23% to 30.5%. Resistance to both agents climbed from 7.5% to 22.3% (P<0.001). No isolates were found to be resistant to any of the other antimicrobial agents. Risk factors for carriage and/or antimicrobial resistance were also assessed.

Anti-Bacterial Agents↗

Arming the enemy: the evolution of resistance to self-proteins.

A remarkable range of novel antibiotics is attracting increasing interest as a major new weapon in the campaign against bacterial infection. They are based on the toxic peptides that provide the innate immune system of animals, and it is claimed that bacteria will be unable to evolve resistance to them because they attack the 'Achilles' heel' of bacterial membrane structure. Both experimental evidence and theoretical arguments suggest that this claim is doubtful. If so, the introduction of these substances into general use may provoke the evolution of resistance to our own defence proteins and thus compromise our natural defences against infection.

Animals↗

[Evolution of resistance to quinolonesin Salmonella enterica in our environment]

Salmonella enterica is mainly associated with acute gastroenteritis; however, it is also associated with other more severe disease processes, for which quinolones are the treatment of choice. We retrospectively studied the evolution of resistance to nalidixic acid and ciprofloxacin of all the clinical isolates of S. enterica from 1992 to 1998 in our hospital environment. A total of 848 strains from feces, blood and other locations were studied. We detected an increase in the resistance to nalidixic acid from 12% in 1992 to 21.3% in 1998, especially in the Enteritidis and Hadar serotypes. We did not detect resistance to ciprofloxacin, but there was in increase in the MIC in the nalidixic acid-resistant strains. Although this is interpreted as sensitive according the the NCCLS criteria, if we apply the cutoff points established by MENSURA, 89.46% of the strains do not fit into this category (S <0.12 mg/l). This puts into question the utility of quinolones in the long-term treatment of severe disease processes produced by this type of strain.

Journal Article↗

[Evolution of resistance to quinolones in Salmonella enterica in our setting].

Salmonella enterica is mainly associated with acute gastroenteritis; however, it is also associated with other more severe disease processes, for which quinolones are the treatment of choice. We retrospectively studied the evolution of resistance to nalidixic acid and ciprofloxacin of all the clinical isolates of S. enterica from 1992 to 1998 in our hospital environment. A total of 848 strains from feces, blood and other locations were studied. We detected an increase in the resistance to nalidixic acid from 12% in 1992 to 21.3% in 1998, especially in the Enteritidis and Hadar serotypes. We did not detect resistance to ciprofloxacin, but there was in increase in the MIC in the nalidixic acid-resistant strains. Although this is interpreted as sensitive according the the NCCLS criteria, if we apply the cutoff points established by MENSURA, 89.46% of the strains do not fit into this category (S <0.12 mg/l). This puts into question the utility of quinolones in the long-term treatment of severe disease processes produced by this type of strain.

Anti-Infective Agents↗

Molecular epidemiology and evolution of resistance to quinolones in Escherichia coli after prolonged administration of ciprofloxacin in patients with prostatitis.

The emergence and evolution of quinolone-resistant Escherichia coli in faeces of patients with prostatitis treated with high-dose oral ciprofloxacin for 1 month were studied. In 11 of 23 patients, from whom only quinolone-susceptible E. coli was isolated before treatment, quinolone-resistant strains, genetically distinct from the quinolone-susceptible ones, predominated during and just after therapy. Two months after treatment, these were completely displaced by quinolone-susceptible E. coli, genetically distinct from the E. coli isolated before and during therapy. Hence, during ciprofloxacin therapy, half of the patients were transiently colonized with new, quinolone-resistant strains of E. coli.

Anti-Infective Agents↗

Intracellular interactions shape antiviral resistance outcomes in poliovirus via eco-evolutionary feedback.

Antiviral resistance evolution poses a major obstacle for controlling viral infections. A promising strategy is to target shared viral proteins that allow drug susceptible viruses to sensitize resistant ones during cellular coinfection, muting selection for resistance. Pocapavir, a poliovirus capsid inhibitor, employs this sociovirological strategy. While susceptible viruses significantly suppressed resistance in the presence of pocapavir in cell culture, a pocapavir clinical trial observed widespread resistance evolution and limited improvements to clearance times. To reconcile these findings, we present an intra-host eco-evolutionary model of poliovirus in the presence of pocapavir, which reproduces both the potent interference observed in vitro and the resistance emergence seen in patients. In the short term, our model predicts that a high density of susceptible viruses sensitizes resistant ones to pocapavir, mirroring cell culture results. However, over multiple replication cycles, pocapavir's high potency collapses viral density, which reduces coinfection and allows resistance to evolve as observed in the clinical trial. Since coinfection is essential to suppress resistance, enabling greater survival of susceptible viruses could offer therapeutic advantages. Counterintuitively, we demonstrate that this can be achieved by lessening antiviral potency, which can limit resistance evolution while also maintaining a low viral load. These findings suggest that antivirals that rely on viral intracellular interaction must balance immediate neutralization with the preservation of future coinfection, yielding more sustained inhibition. Explicitly considering the eco-evolutionary feedback encompassing viral density, shared phenotypes and absolute fitness not only provides new insights into designing effective therapies but also illuminates viral evolutionary dynamics more broadly.

Journal Article↗

Evolution of resistance to cancer therapy.

Acquired drug resistance is a major limitation for successful treatment of cancer. Resistance emerges due to drug exclusion, drug metabolism and alteration of the drug target by mutation or overexpression. Depending on therapy, the type of cancer and its stage, one or several genetic or epigenetic alterations are necessary to confer resistance to treatment. The fundamental question is the following: if a genetically diverse population of replicating cancer cells is subjected to chemotherapy that has the potential to eradicate it, what is the probability of emergence of resistance? Here, we review a general mathematical framework based on multi-type branching processes designed to study the dynamics of escape of replicating organisms from selection pressures. We apply the general model to evolution of resistance of cancer cells and discuss examples for diverse mechanisms of resistance. Our theory shows how to estimate the probability of success for any treatment regimen.

Animals↗

Experimental evolution of resistance in Paramecium caudatum against the bacterial parasite Holospora undulata.

Host-parasite coevolution is often described as a process of reciprocal adaptation and counter adaptation, driven by frequency-dependent selection. This requires that different parasite genotypes perform differently on different host genotypes. Such genotype-by-genotype interactions arise if adaptation to one host (or parasite) genotype reduces performance on others. These direct costs of adaptation can maintain genetic polymorphism and generate geographic patterns of local host or parasite adaptation. Fixation of all-resistant (or all-infective) genotypes is further prevented if adaptation trades off with other host (or parasite) life-history traits. For the host, such indirect costs of resistance refer to reduced fitness of resistant genotypes in the absence of parasites. We studied (co)evolution in experimental microcosms of several clones of the freshwater protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. After two and a half years of culture, inoculation of evolved and naive (never exposed to the parasite) hosts with evolved and founder parasites revealed an increase in host resistance, but not in parasite infectivity. A cross-infection experiment showed significant host clone-by-parasite isolate interactions, and evolved hosts tended to be more resistant to their own (local) parasites than to parasites from other hosts. Compared to naive clones, evolved host clones had lower division rates in the absence of the parasite. Thus, our study indicates de novo evolution of host resistance, associated with both direct and indirect costs. This illustrates how interactions with parasites can lead to the genetic divergence of initially identical populations.

Animals↗

Endogenous retroviruses and the evolution of resistance to retroviral infection.

The current AIDS epidemic has rekindled interest in the evolution of retroviruses and the development of resistance to infection. Retroviruses and their vertebrate hosts have coexisted for millions of years, during which time a variety of host defence mechanisms has evolved. One repeated strategy is to use endogenous retroviruses to combat infection by their exogenous relatives.

Animals↗