Author
Diarmaid Hughes
Other affiliations: ICM Partners, Trinity College, Dublin, University of California, Davis
Bio: Diarmaid Hughes is an academic researcher from Uppsala University. The author has contributed to research in topics: Gene & Mutant. The author has an hindex of 45, co-authored 167 publications receiving 11221 citations. Previous affiliations of Diarmaid Hughes include ICM Partners & Trinity College, Dublin.
Topics: Gene, Mutant, Antibiotic resistance, Mutation, Drug resistance
Papers published on a yearly basis
Papers
More filters
TL;DR: The findings suggest that the fitness costs of resistance will allow susceptible bacteria to outcompete resistant bacteria if the selective pressure from antibiotics is reduced, and that the rate of reversibility will be slow at the community level.
Abstract: Most antibiotic resistance mechanisms are associated with a fitness cost that is typically observed as a reduced bacterial growth rate. The magnitude of this cost is the main biological parameter that influences the rate of development of resistance, the stability of the resistance and the rate at which the resistance might decrease if antibiotic use were reduced. These findings suggest that the fitness costs of resistance will allow susceptible bacteria to outcompete resistant bacteria if the selective pressure from antibiotics is reduced. Unfortunately, the available data suggest that the rate of reversibility will be slow at the community level. Here, we review the factors that influence the fitness costs of antibiotic resistance, the ways by which bacteria can reduce these costs and the possibility of exploiting them.
1,929 citations
TL;DR: It is suggested that the low antibiotic concentrations found in many natural environments are important for enrichment and maintenance of resistance in bacterial populations.
Abstract: The widespread use of antibiotics is selecting for a variety of resistance mechanisms that seriously challenge our ability to treat bacterial infections. Resistant bacteria can be selected at the high concentrations of antibiotics used therapeutically, but what role the much lower antibiotic concentrations present in many environments plays in selection remains largely unclear. Here we show using highly sensitive competition experiments that selection of resistant bacteria occurs at extremely low antibiotic concentrations. Thus, for three clinically important antibiotics, drug concentrations up to several hundred-fold below the minimal inhibitory concentration of susceptible bacteria could enrich for resistant bacteria, even when present at a very low initial fraction. We also show that de novo mutants can be selected at sub-MIC concentrations of antibiotics, and we provide a mathematical model predicting how rapidly such mutants would take over in a susceptible population. These results add another dimension to the evolution of resistance and suggest that the low antibiotic concentrations found in many natural environments are important for enrichment and maintenance of resistance in bacterial populations.
1,308 citations
TL;DR: The ecology of antibiotics and the ability of subinhibitory concentrations to select for bacterial resistance are discussed and the effects of low-level drug exposure on bacterial physiology are considered, including the generation of genetic and phenotypic variability, as well as the able of antibiotics to function as signalling molecules.
Abstract: The widespread use of antibiotics results in the generation of antibiotic concentration gradients in humans, livestock and the environment. Thus, bacteria are frequently exposed to non-lethal (that is, subinhibitory) concentrations of drugs, and recent evidence suggests that this is likely to have an important role in the evolution of antibiotic resistance. In this Review, we discuss the ecology of antibiotics and the ability of subinhibitory concentrations to select for bacterial resistance. We also consider the effects of low-level drug exposure on bacterial physiology, including the generation of genetic and phenotypic variability, as well as the ability of antibiotics to function as signalling molecules. Together, these effects accelerate the emergence and spread of antibiotic-resistant bacteria among humans and animals.
1,226 citations
TL;DR: Routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system, as well as the ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis.
484 citations
TL;DR: The results suggest that bacterial evolution to reduce the costs of antibiotic resistance can take different trajectories within and outside a host.
Abstract: Most types of antibiotic resistance impose a biological cost on bacterial fitness. These costs can be compensated, usually without loss of resistance, by second-site mutations during the evolution of the resistant bacteria in an experimental host or in a laboratory medium. Different fitness-compensating mutations were selected depending on whether the bacteria evolved through serial passage in mice or in a laboratory medium. This difference in mutation spectra was caused by either a growth condition-specific formation or selection of the compensated mutants. These results suggest that bacterial evolution to reduce the costs of antibiotic resistance can take different trajectories within and outside a host.
452 citations
Cited by
More filters
European Centre for Disease Prevention and Control1, Centers for Disease Control and Prevention2, Tel Aviv Sourasky Medical Center3, Tufts University4, ALFA5, Karolinska University Hospital6, University of Geneva7, University of California, Los Angeles8, Royal Brisbane and Women's Hospital9, Brown University10, Brigham and Women's Hospital11
TL;DR: A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control and the Centers for Disease Control and Prevention, to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp.
8,695 citations
TL;DR: This review brings up important questions that are still open, and addresses some significant issues which must be tackled in the future for a better understanding of the behavior of antibiotics in the environment, as well as the risks associated with their occurrence.
3,620 citations
Journal Article•
3,097 citations
TL;DR: The antibacterial mechanisms of NPs against bacteria and the factors that are involved are discussed and the limitations of current research are discussed.
Abstract: Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed.
2,178 citations
TL;DR: The findings suggest that the fitness costs of resistance will allow susceptible bacteria to outcompete resistant bacteria if the selective pressure from antibiotics is reduced, and that the rate of reversibility will be slow at the community level.
Abstract: Most antibiotic resistance mechanisms are associated with a fitness cost that is typically observed as a reduced bacterial growth rate. The magnitude of this cost is the main biological parameter that influences the rate of development of resistance, the stability of the resistance and the rate at which the resistance might decrease if antibiotic use were reduced. These findings suggest that the fitness costs of resistance will allow susceptible bacteria to outcompete resistant bacteria if the selective pressure from antibiotics is reduced. Unfortunately, the available data suggest that the rate of reversibility will be slow at the community level. Here, we review the factors that influence the fitness costs of antibiotic resistance, the ways by which bacteria can reduce these costs and the possibility of exploiting them.
1,929 citations