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 19 recordsLinked to original sources
PubMed2025

Reflecting on Fleming's caveat: the impact of stakeholder decision-making on antimicrobial resistance evolution.

Antimicrobial resistance poses one of the greatest and most imminent threats to global health, environment and food security, for which an urgent response is mandated. Evolutionary approaches to tackling the crisis tend to focus on proximate issues including the mechanisms and pathways to resistance, with associated calls to action for infection control and antimicrobial stewardship. This is of clear benefit but overlooks the fundamental influence of policy and stakeholder decision-making on resistance evolution. In 1945, Fleming issued a stark warning on the irresponsible use of penicillin and its potential to cause death due to penicillin-resistant infections. Attention to resistance evolution theory and heeding Fleming's advice could have allowed for a vastly different reality. Embedding evolutionary theory within policy, industry and regulatory bodies is not only essential but is now a race against time. Hence, critical appraisal of historical behaviour and attitudes at a global scale can inform a paradigm of anticipatory and adaptive policy. To undertake this exercise, we focused on the largest group of antibiotics with the greatest clinical and economic footprint, the beta-lactams. We examined historical case studies that affected how beta-lactams were developed, produced, approved and utilized, in order to relate stakeholder decision-making to resistance evolution. We derive lessons from these observations and propose sustainable approaches to curb resistance evolution. We set a position that actively incorporates an evolutionary theory of antimicrobial resistance into decision-making within antimicrobial development, production and stewardship.

Anti-Bacterial Agents↗
PubMed1990

DNA probes for studying streptothricin resistance evolution in enteric bacteria.

Probes for the detection of streptothricin resistance genes have been derived from recombinant plasmids. These include the streptothricin resistance gene probe sat 1/2 derived from Tn 1826 and specific for both the sat-1 determinant of Tn 1825 and the sat-2 determinant of Tn 1826, and the probe sat D derived from and specific for the sat-1 determinant of transposon Tn 1825. A third streptothricin resistance gene probe, sat 3, represents the streptothricin resistance determinant sat-3 of the IncQ R plasmid pIE639. Hybridization studies did not reveal any sequence homology between sat-3 and the transposon-localized sat-1 and sat-2 determinants. Moreover, non of the different sat-determinants isolated from plasmids of gram negative bacteria hybridized with the analogous resistance determinant of Streptomyces noursei, which had been cloned and named nat by Krügel et al. (Gene, 1988, 62, 209-214). The sat 1/2 probe in combination with the sat D probe proved to be suitable for the identification and the differentiation of sat-1 and sat-2 determinants in different genetic environments. Streptothricin resistance genes related to those present on transposons Tn 1825 and Tn 1826 have been detected by hybridization with the probe sat 1/2 on plasmids isolated a long time ago before the application of streptothricins. The sat-3 determinant appears to be exclusively associated with the IncQ plasmid pIE639.

Aminoglycosides↗
PubMed2025

Effects of recombination on multi-drug resistance evolution in Plasmodium falciparum malaria.

When multiple beneficial alleles at multiple loci are present in a population but not linked together in any one individual, there is no general evolutionary result that determines whether recombination will speed up or slow down the emergence and evolution of genotypes carrying multiple beneficial alleles. Translated to infectious disease control, this evolutionary uncertainty means that when multiple types of drug resistance are present we do not know whether recombination will act more strongly to (1) bring together single-resistant genotypes into multi-drug resistant (MDR) genotypes, or (2) break apart MDR genotypes into single-resistant genotypes. In this paper, we introduce a new version of an established and validated individual-based malaria transmission model where we have added 25 drug-resistance related loci, individual mosquito bites, and mosquitoes feeding on multiple hosts in a single meal (interrupted feeds) allowing for recombination events of different Plasmodium falciparum genotypes from different hosts. Recombination among P. falciparum genotypes in this model occurs from two sources of variation, multi-clonal infections in single hosts and interrupted feeds on multiple hosts, and we show that 80% to 97% of MDR recombinant falciparum genotypes are projected to occur from single uninterrupted bites on hosts with multi-clonal infections (for malaria prevalence > 5%). Increases in the model's interrupted feeding rate slowly increase the number of recombination events occurring from interrupted feeds. A comparison of drug-resistance management strategies with this new model shows that, over a 15-year timeframe, triple artemisinin-combination therapies (ACT) strategies show the largest reductions in treatment failures and the longest delays until artemisinin resistance reaches a critical 1% threshold. Multiple first-line therapies (MFT) are second best under these criteria, and ACT cycling approaches are third best. When compared to cycling strategies, MFT strategies generate a greater diversity of recombinant genotypes but fewer recombination events generating MDR and slower emergence of these recombinant MDR genotypes.

Plasmodium falciparum↗
PubMed1989

Evolution of resistance with sequential application of insecticides in time and space.

The effect, on the evolution of resistance, of alternating two unrelated insecticides in space or in time (or both) is studied. Transient polymorphism is shown to occur under certain conditions of mating, selection and migration. In some situations, the transient polymorphism can show a sharp decline before the alleles recover to fixation. Alternating a single insecticide in space, and in space and time, is also considered. Neither alternation in space nor in time shows any advantage with regard to delaying the onset of resistance. The most promising mode is to alternate the presence and absence of a single insecticide in both space and time, especially if it is applied at the larval stage and if some form of biological control is used in the regions where no insecticide is applied.

Animals↗
PubMed1985

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↗
PubMed2025

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↗
PubMed1979

Dichlorophenylurea-resistant oxygen evolution in Chlorella after cerulenin treatment.

Fluorescence spectra at 77 K, oxygen evolution at 30 degrees C and delayed fluorescence at 25 degrees C were measured in Chlorella pyrenoidosa cultures with and without cerulenin and subsequent 3-(3,4-dichlorophenyl)-1,1-dimethyl-urea (DCMU) treatment, respectively. In pure algal cultures the oxygen evolution was inhibited by DCMU and the long-time component of fluorescence was highly influenced by DCMU, as expected. In contrast, both oxygen evolution and delayed fluorescence became DCMU-resistant in cerulenin-treated cultures. The DCMU-resistance is correlated with a change in the fatty acid distribution of the thylakoid membrane, which also leads to changes in the prompt fluorescence. Cerulenin appears to be a promising new tool of diagnostics for the hitherto unsatisfactorily understood processes of oxygen evolution in photosynthesizing organisms.

Antifungal Agents↗
PubMed1988

[Comparative activity of habekacin and 4 other aminoglycosides against gram-negative bacilli. Evolution of resistance].

The activity of 5 aminoglycosides compounds (habekacin, amikacin, gentamicin, netilmicin and tobramycin) was studied by an agar dilution method, against 235 strains of Enterobacteriaceae and 146 other Gram negative bacilli. 79 to 98% of susceptible strains were observed, according to the aminoglycoside compound. Habekacin and amikacin were the most effective, specially against the more frequently resistant bacteria: Enterobacter, Serratia, Hafnia, Acinetobacter, Pseudomonas aeruginosa. In comparison with a previous study, no evolution was observed in the resistance to aminoglycosides.

Acinetobacter↗
PubMed2026

Understanding Candidozyma (Candida) auris: genomic evolution, antifungal resistance and the growing challenges in global infection control.

Candida auris (recently renamed Candidozyma auris) is an emerging multidrug-resistant fungal pathogen, first identified in Japan in 2009. C. auris exhibits remarkable persistence on human skin and inanimate surfaces, resistance to multiple antifungals, notably fluconazole, and biofilm formation, which hinders infection control and leads to hospital outbreaks with high mortality rates. Despite ongoing research, key aspects of its reservoir origin, transmission routes and the best way to combat its spread and multidrug resistance remain unclear. Improving genomic surveillance and antifungal strategies is crucial to contain its spread and mitigate the growing public health threat posed by this resilient and potentially fatal fungal pathogen.

Humans↗
PubMed2026

Single unscreened carrier triggered ICU outbreak of a KPC-producing Klebsiella pneumoniae which acquired in vivo resistance to ceftazidime-avibactam, and cefiderocol.

BACKGROUND: Carbapenemase-producing Enterobacterales are a major cause of healthcare-associated outbreaks in intensive care units (ICUs), where unrecognized carriers can drive silent transmission. We report an ICU outbreak caused by KPC-producing Klebsiella pneumoniae and the within-host emergence of resistance to ceftazidime-avibactam and cefiderocol in the index case. METHODS: Four ICU patients with five K. pneumoniae isolates identified between July and August 2023 were investigated. Phenotypic, genomic and functional analyses were performed to determine the clonal relatedness of the isolates and elucidate the mechanisms underlying resistance evolution. RESULTS: All isolates belonged to ST512, confirming dissemination of a single high-risk clone. The first isolate recovered from the index patient was susceptible to ceftazidime-avibactam and cefiderocol, but a later isolate obtained during ceftazidime-avibactam therapy acquired resistance to both agents. Genomic analysis revealed a novel KPC variant (KPC-270) carrying a 19-amino-acid duplication. When expressed in Escherichia coli, KPC-270 conferred ceftazidime-avibactam resistance, but it did not fully reproduce the meropenem or cefiderocol phenotype. Efflux inhibition substantially reduced meropenem and cefiderocol MICs in the resistant isolate, and avibactam partially restored cefiderocol activity, supporting multifactorial mechanism. CONCLUSION: This outbreak illustrates how unrecognized multidrug-resistant carriage in the index patient facilitated the nosocomial dissemination of a high-risk ST512 K. pneumoniae clone, followed by rapid resistance evolution during ceftazidime-avibactam therapy. Resistance was multifactorial, involving the novel KPC-270 variant and efflux activity contributing to ceftazidime-avibactam, meropenem and cefiderocol resistance.

Cefiderocol↗
PubMed2024

Decoding the trajectory of antibiotic resistance genes in saline and alkaline soils: Insights from different fertilization regimes.

The soil salinity and alkalinity play an important role in the occurrence and proliferation of antibiotic resistance genes (ARGs). Yet, little is known the underlying mechanism by which soil salinity and alkalinity affect antibiotic resistance evolution. Here we investigated the ARGs variation in soil salinity and alkalinity environments created by different fertilization, and explored the biological mechanisms that salinity and alkalinity alter the evolutionary paradigm of antibiotic resistance. The results showed the soil treated by organic fertilizer exhibited a low salinity, neutral level (TSD 239.20 μS/cm, pH 7.17). The ARG abundance in the OF treatment was the highest, keeping an average of 67.83 TPM. Beside the effect of direct input of organic fertilizer at the beginning, it was important to note that, ARGs abundance during planting showed significant correlations with pH and electric conductivity. We observed that changes in microbial survival strategies under different salinity and alkalinity conditions further affected ARG hosts abundance. Indoor experiments demonstrated that there was a survival trade-off between the growth of resistant bacteria and the evolution of antibiotic resistance in salinity and alkalinity environments. Meta-genomic and Meta-transcriptomic analysis consistently demonstrated bacterial antibiotic resistance was primarily associated with pyruvate, energy and lipid metabolic pathways. The functional gene related to salinity and alkalinity, like cysH, cysK, plsB and plsC showed negative correlations with MDR. Prokaryotic transcription assays validated these relations. This study well explains the prevalence of soil ARGs after different fertilization regimes and will give a deeper understanding for the effect of soil salinity and alkalinity on antibiotic resistance evolution.

Soil↗
PubMed1985

R1767, an example of the evolution of resistance plasmids.

The Salmonella R-factor system R1767 undergoes frequent rearrangement of its plasmid components. The flux of genetic material within this plasmid system depends on a combination of illegitimate and homologous recombination. The presence of several copies of IS160 and two multiresistance transposons, Tn2410 and Tn2411, are substantial reasons for the observed variations.

Biological Evolution↗