# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 4060 | 0 | 0.9988 | Current status of antibiotic resistance in animal production. It is generally accepted that the more antibiotics we use, the faster bacteria will develop resistance. Further it has been more or less accepted that once an antibiotic is withdrawn from the clinic, the resistance genes will eventually disappear, [table: see text] since they will no more be of any survival value for the bacterial cell. However, recent research has shown that after a long time period of exposure to antibiotics, certain bacterial species may adapt to this environment in such a way that they keep their resistance genes stably also after the removal of antibiotics. Thus, there is reason to believe that once resistance has developed it will not even in the long term be eradicated. What then can we do not to increase further the already high level of antibiotic-resistant bacteria in animals? We should of course encourage a prudent use of these valuable drugs. In Sweden antibiotics are not used for growth promoting purposes and are available only after veterinary prescription on strict indications. Generally, antimicrobial treatment of animals on individual or on herd basis should not be considered unless in connection with relevant diagnostics. The amounts of antibiotics used and the development of resistance in important pathogens should be closely monitored. Furthermore, resistance monitoring in certain non-pathogenic intestinal bacteria, which may serve as a reservoir for resistance genes is probably more important than hitherto anticipated. Once the usage of or resistance to a certain antibiotic seems to increase in an alarming way, steps should be taken to limit the usage of the drug in order to prevent further spread of resistance genes in animals, humans and the environment. Better methods for detecting and quantifying antibiotic resistance have to be developed. Screening methods must be standardized and evaluated in order to obtain comparable and reliable results from different countries. The genetic mechanisms for development of resistance and spread of resistance genes should be studied in detail. Research in these areas will lead to new ideas on how to inhibit the resistance mechanisms. So far, it has been well established that a heavy antimicrobial drug selective pressure in overcrowded populations of production animals creates favourable environments both for the emergence and the spread of antibiotic resistance genes. | 1999 | 10783714 |
| 9383 | 1 | 0.9987 | The cost of antibiotic resistance--from the perspective of a bacterium. The possession of an antibiotic resistance gene clearly benefits a bacterium when the corresponding antibiotic is present. But does the resistant bacterium suffer a cost of resistance (i.e. a reduction in fitness) when the antibiotic is absent? If so, then one strategy to control the spread of resistance would be to suspend the use of a particular antibiotic until resistant genotypes declined to low frequency. Numerous studies have indeed shown that resistant genotypes are less fit than their sensitive counterparts in the absence of antibiotic, indicating a cost of resistance. But there is an important caveat: these studies have put antibiotic resistance genes into naïve bacteria, which have no evolutionary history of association with the resistance genes. An important question, therefore, is whether bacteria can overcome the cost of resistance by evolving adaptations that counteract the harmful side-effects of resistance genes. In fact, several experiments have shown that the cost of antibiotic resistance may be substantially diminished, even eliminated, by evolutionary changes in bacteria over rather short periods of time. As a consequence of this adaptation of bacteria to their resistance genes, it becomes increasingly difficult to eliminate resistant genotypes simply by suspending the use of antibiotics. | 1997 | 9189639 |
| 4116 | 2 | 0.9987 | Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data. The use of antibiotics in food animals selects for bacteria resistant to antibiotics used in humans, and these might spread via the food to humans and cause human infection, hence the banning of growth-promoters. The actual danger seems small, and there might be disadvantages to human and to animal health. The low dosages used for growth promotion are an unquantified hazard. Although some antibiotics are used both in animals and humans, most of the resistance problem in humans has arisen from human use. Resistance can be selected in food animals, and resistant bacteria can contaminate animal-derived food, but adequate cooking destroys them. How often they colonize the human gut, and transfer resistance genes is not known. In zoonotic salmonellosis, resistance may arise in animals or humans, but human cross-infection is common. The case of campylobacter infection is less clear. The normal human faecal flora can contain resistant enterococci, but indistinguishable strains in animals and man are uncommon, possibly because most animal enterococci do not establish themselves in the human intestine. There is no correlation between the carriage of resistant enterococci of possible animal origin and human infection with resistant strains. Commensal Escherichia coli also exhibits host-animal preferences. Anti-Gram-positive growth promoters would be expected to have little effect on most Gram-negative organisms. Even if resistant pathogens do reach man, the clinical consequences of resistance may be small. The application of the 'precautionary principle' is a non-scientific approach that assumes that risk assessments will be carried out. | 2004 | 14657094 |
| 9384 | 3 | 0.9987 | Bacterial evolution and the cost of antibiotic resistance. Bacteria clearly benefit from the possession of an antibiotic resistance gene when the corresponding antibiotic is present. But do resistant bacteria suffer a cost of resistance (i.e., a reduction in fitness) when the antibiotic is absent? If so, then one strategy to control the spread of resistance would be to suspend the use of a particular antibiotic until resistant genotypes declined to low frequency. Numerous studies have indeed shown that resistant genotypes are less fit than their sensitive counterparts in the absence of antibiotic, indicating a cost of resistance. But there is an important caveat: these studies have put resistance genes into naive bacteria, which have no evolutionary history of association with the resistance genes. An important question, therefore, is whether bacteria can overcome the cost of resistance by evolving adaptations that counteract the harmful side-effects of resistance genes. In fact, several experiments (in vitro and in vivo) show that the cost of antibiotic resistance can be substantially diminished, even eliminated, by evolutionary changes in bacteria over rather short periods of time. As a consequence, it becomes increasingly difficult to eliminate resistant genotypes simply by suspending the use of antibiotics. | 1998 | 10943373 |
| 9687 | 4 | 0.9987 | Spread of organisms with novel genotypes: thoughts from an ecological perspective. One category of objection to the release of organisms produced by genetic engineering is based on the fear that such organisms may persist in the environment and damage existing ecosystems. An assessment of environmental risk thus involves an ecological question analogous to the introduction of exotic species which has been known to produce serious ecological disruptions. An investigation of the literature on exotic introductions reveals, however, that foreign species do not invariably produce adverse changes. Ecologists believe that only a fraction of immigrating species actually produces ecological dislocation while the majority probably fail to penetrate existing biotic assemblages. Stressed or simplified environments are, however, more vulnerable to successful invasion. Unfortunately, because very little information has ever been collected to document the number or causes of failed introductions, it is impossible to quantify the probability that any introduced species will or will not cause serious disturbance purely on the basis of historical evidence. The development and spread of genotypes that confer resistance to chemical control agents in insects and microorganisms is also analogous to genetic engineering in that human activity contributes to the spread of new genotypes. In both groups of organisms, resistant genotypes can come to predominate in even geographically widespread populations with great rapidity. Resistance to pesticides in insects is usually found to be determined by single genes. In bacteria, antibiotic resistance genes are usually, if not always, associated with the extrachromosomal genetic elements known as plasmids. Bacteria seem to be able to transmit plasmid-borne genes between species and genera with facility. The ease with which new genes can be inserted into bacteria via plasmid vectors in recombinant technology is thus a two-edged sword. It may be very difficult to keep inserted genes isolated in single bacterial strains. The evaluation of the literature on which this report is based suggests that an ecological approach for risk assessment is appropriate. Microorganisms, for which genetic engineering is of most immediate importance, exhibit the same ecological properties as higher organisms. The proportion of an organism's genome which is novel has no direct correlation with the magnitude of impact such a change may have in economic, medical, or ecological terms. Meaningful probabilities for persistence of engineered organisms in the environment will have to be generated by experiment, probably with model microbial ecosystems. | 1983 | 6576449 |
| 8927 | 5 | 0.9987 | Changes in Intrinsic Antibiotic Susceptibility during a Long-Term Evolution Experiment with Escherichia coli. High-level resistance often evolves when populations of bacteria are exposed to antibiotics, by either mutations or horizontally acquired genes. There is also variation in the intrinsic resistance levels of different bacterial strains and species that is not associated with any known history of exposure. In many cases, evolved resistance is costly to the bacteria, such that resistant types have lower fitness than their progenitors in the absence of antibiotics. Some longer-term studies have shown that bacteria often evolve compensatory changes that overcome these tradeoffs, but even those studies have typically lasted only a few hundred generations. In this study, we examine changes in the susceptibilities of 12 populations of Escherichia coli to 15 antibiotics after 2,000 and 50,000 generations without exposure to any antibiotic. On average, the evolved bacteria were more susceptible to most antibiotics than was their ancestor. The bacteria at 50,000 generations tended to be even more susceptible than after 2,000 generations, although most of the change occurred during the first 2,000 generations. Despite the general trend toward increased susceptibility, we saw diverse outcomes with different antibiotics. For streptomycin, which was the only drug to which the ancestral strain was highly resistant, none of the evolved lines showed any increased susceptibility. The independently evolved lineages often exhibited correlated responses to the antibiotics, with correlations usually corresponding to their modes of action. On balance, our study shows that bacteria with low levels of intrinsic resistance often evolve to become even more susceptible to antibiotics in the absence of corresponding selection.IMPORTANCE Resistance to antibiotics often evolves when bacteria encounter antibiotics. However, bacterial strains and species without any known exposure to these drugs also vary in their intrinsic susceptibility. In many cases, evolved resistance has been shown to be costly to the bacteria, such that resistant types have reduced competitiveness relative to their sensitive progenitors in the absence of antibiotics. In this study, we examined changes in the susceptibilities of 12 populations of Escherichia coli to 15 antibiotics after 2,000 and 50,000 generations without exposure to any drug. The evolved bacteria tended to become more susceptible to most antibiotics, with most of the change occurring during the first 2,000 generations, when the bacteria were undergoing rapid adaptation to their experimental conditions. On balance, our findings indicate that bacteria with low levels of intrinsic resistance can, in the absence of relevant selection, become even more susceptible to antibiotics. | 2019 | 30837336 |
| 9502 | 6 | 0.9987 | Bacterial resistance to disinfectants: present knowledge and future problems. Bacterial resistance to antibiotics is a long-established, widely-studied problem. Increasingly, attention is being directed to the responses of various types of microbes to biocides (antiseptics, disinfectants and preservatives). Different groups of bacteria vary in their susceptibility to biocides, with bacterial spores being the most resistant, followed by mycobacteria, then Gram-negative organisms, with cocci generally being the most sensitive. There are wide divergencies within this general classification. Thus, (i) spores of Bacillus subtilis are less susceptible to biocides than those of Clostridium difficile: (ii) Mycobacterium chelonae strains may show high resistance to glutaraldehyde and M. avium intracellulare is generally less sensitive than M. tuberculosis; (iii) Gram-negative bacteria such as Pseudomonas aeruginosa, Providencia spp and Proteus spp may be difficult to inactivate; (iv) enterococci are less sensitive than staphylococci to biocides and antibiotic-resistant strains of Staphylococcus aureus might show low-level biocide resistance. The mechanisms involved in biocide resistance to biocides are becoming better understood. Intrinsic resistance (intrinsic insusceptibility) is found with bacterial spores, mycobacteria and Gram-negative bacteria. This resistance might, in some instances, be associated with constitutive degradative enzymes but in reality is more closely linked to cellular impermeability. The coats(s) and, to some extent, the cortex in spores, the arabinogalactan and possibly other components of the mycobacterial cell wall and the outer membrane of Gram-negative bacteria limit the concentration of active biocide that can reach the target site(s) in these bacterial cells. A special situation is found with bacteria present in biofilms, which can be considered as being an intrinsic resistance mechanism resulting from physiological (phenotypic) adaptation of cells. Acquired resistance to biocides may arise by cellular mutation or by the acquisition of genetic elements. Plasmid/transposon-mediated resistance to inorganic and organic mercury compounds by hydrolases and reductases has been extensively studied. Plasmid-mediated resistance to some other biocides in Gram-negative bacteria and in staphylococci has been described, but its significance remains uncertain. As to the future, there is a need to establish conclusively whether there is a clear-cut linkage between antibiotic and biocide resistance in non-sporulating bacteria and whether biocides can select for antibiotic resistance. Additionally, the responses to biocides of new and emerging pathogens must be assessed. At the same time, continuing research is necessary to establish further the underlying mechanisms of resistance and to provide more efficient means of bacterial inactivation. | 1999 | 10658759 |
| 3822 | 7 | 0.9987 | Development of resistance following the use of antibiotics. There is no doubt that antibiotic usage is related to the development of resistant bacteria. Nevertheless, there is a great deal of confusion about the mechanisms involved in this process and the quantitative aspects. Bacterial genes coding for resistance can be exchanged on a molecular level between different DNA structures and they can spread from one bacterial cell to another. In quantitative terms, however, the selection of resistant bacteria in their natural environment, e.g. in the bowel flora or on mucous membranes, is the most important factor influencing the development and spread of antibiotic resistant microorganisms. The amount of drug incorporated into the bowel or soft tissue flora depends on the route of administration. Even drugs which are related in many respects differ markedly in their ability to select resistant organisms. A selection of resistant organisms from the normal human flora implicates, that primarily a minority of resistant organisms is present and overgrows the sensitive ones which are inhibited by the drug. Usually these resistant strains belong to the resident flora and carry their resistance genes on plasmids. Only rarely resistant mutants can be found, although the mutation rate might be high. The development of resistance from the population of microorganisms causing the infection is rare. This observation can be based on two rationales : 1. The mutation rate from susceptible to resistant in most microorganisms is usually rather low (about 10(-9); thus the number of microbes present on the site of infection is not high enough to allow mutants to arise.(ABSTRACT TRUNCATED AT 250 WORDS) | 1984 | 6588480 |
| 4391 | 8 | 0.9987 | 'To be, or not to be'-The dilemma of 'silent' antimicrobial resistance genes in bacteria. Antimicrobial resistance is a serious threat to public health that dramatically undermines our ability to treat bacterial infections. Microorganisms exhibit resistance to different drug classes by acquiring resistance determinants through multiple mechanisms including horizontal gene transfer. The presence of drug resistance genotypes is mostly associated with corresponding phenotypic resistance against the particular antibiotic. However, bacterial communities harbouring silent antimicrobial resistance genes-genes whose presence is not associated with a corresponding resistant phenotype do exist. Under suitable conditions, the expression pattern of such genes often revert and regain resistance and could potentially lead to therapeutic failure. We often miss the presence of silent genes, since the current experimental paradigms are focused on resistant strains. Therefore, the knowledge on the prevalence, importance and mechanism of silent antibiotic resistance genes in bacterial pathogens are very limited. Silent genes, therefore, provide an additional level of complexity in the war against drug-resistant bacteria, reminding us that not only phenotypically resistant strains but also susceptible strains should be carefully investigated. In this review, we discuss the presence of silent antimicrobial resistance genes in bacteria, their relevance and their importance in public health. | 2022 | 35882476 |
| 4115 | 9 | 0.9987 | Antibiotic Use for Growth Promotion in Animals: Ecologic and Public Health Consequences. Antibiotics have successfully treated infectious diseases in man, animals and agricultural plants. However, one consequence of usage at any level, subtherapeutic or therapeutic, has been selection of microorganisms resistant to these valuable agents. Today clinicians worldwide face singly resistant and multiply resistant bacteria which complicate treatment of even common infectious agents. This situation calls for a critical evaluation of the numerous ways in which antibiotics are being used so as to evaluate benefits and risks. About half of the antibiotics produced in the United States arc used in animals, chiefly in subtherapeutic amounts for growth promotion. This usage is for prolonged periods leading to selection of multiply-resistant bacteria which enter a common environmental pool. From there, resistance determinants from different sources spread from one bacterium to another, from one animal host to another, from one area to another. The same resistance determinants have been traced to many different genera associated with humans, animals and foods where they pose a continued threat to public health. Since alternative measures for growth promotion, such as antimicrobials which are not used for human therapy and which do not select for multiple-resistances are available, their use, instead of antibiotics, would remove a major factor contributing to the environmental pool of transferable resistance genes. | 1987 | 30965484 |
| 9438 | 10 | 0.9987 | The challenge of antibiotic resistance: need to contemplate. "Survival of the fittest " holds good for men and animals as also for bacteria. A majority of bacteria in nature are nonpathogenic, a large number of them, live as commensals on our body leading a symbiotic existence. A limited population of bacteria which has became pathogenic was also sensitive to antibiotics to begin with. It is the man made antibiotic pressure, which has led to the emergence and spread of resistant genes amongst bacteria. Despite the availability of a large arsenal of antibiotics, the ability of bacteria to become resistant to antibacterial agents is amazing. This is more evident in the hospital settings where the antibiotic usage is maximum. The use of antibiotics is widespread in clinical medicine, agriculture, aquaculture, veterinary practice, poultry and even in household products. The major reason for this is the inappropriate use of antibiotics due to a lack of uniform policy and disregard to hospital infection control practices. The antibiotic cover provided by newer antibiotics has been an important factor responsible for the emergence of multi-drug resistant bacteria. Bacterial infections increase the morbidity and mortality, increase the cost of treatment, and prolong hospital stay adding to the economical burden on the nation. The problem is further compounded by the lack of education and " over the counter " availability of antibiotics in developing countries. Antibiotic resistance is now all pervasive with the developed world as much vulnerable to the problem. Despite advancement in medical technology for diagnosis and patient care, a person can still die of an infection caused by a multi-drug resistant bacteria. It is time to think, plan and formulate a strong antibiotic policy to address the burgeoning hospital infection. | 2005 | 15756040 |
| 4063 | 11 | 0.9987 | The 2000 Garrod lecture. Factors impacting on the problem of antibiotic resistance. Antibiotic resistance has become a major clinical and public health problem within the lifetime of most people living today. Confronted by increasing amounts of antibiotics over the past 60 years, bacteria have responded to the deluge with the propagation of progeny no longer susceptible to them. While it is clear that antibiotics are pivotal in the selection of bacterial resistance, the spread of resistance genes and of resistant bacteria also contributes to the problem. Selection of resistant forms can occur during or after antimicrobial treatment; antibiotic residues can be found in the environment for long periods of time after treatment. Besides antibiotics, there is the mounting use of other agents aimed at destroying bacteria, namely the surface antibacterials now available in many household products. These too enter the environment. The stage is thus set for an altered microbial ecology, not only in terms of resistant versus susceptible bacteria, but also in terms of the kinds of microorganisms surviving in the treated environment. We currently face multiresistant infectious disease organisms that are difficult and, sometimes, impossible to treat successfully. In order to curb the resistance problem, we must encourage the return of the susceptible commensal flora. They are our best allies in reversing antibiotic resistance. | 2002 | 11751763 |
| 9467 | 12 | 0.9987 | To give or not to give antibiotics is not the only question. In a 1945 Nobel Lecture, Sir Alexander Fleming warned against the overuse of antibiotics, particularly in response to public pressure. In the subsequent decades, evidence has shown that bacteria can become resistant to almost any available molecule. One key question is how the emergence and dissemination of resistant bacteria or resistance genes can be delayed. Although some clinicians remain sceptical, in this Personal View, we argue that the prescription of fewer antibiotics and shorter treatment duration is just as effective as longer regimens that remain the current guideline. Additionally, we discuss the fact that shorter antibiotic treatments exert less selective pressure on microorganisms, preventing the development of resistance. By contrast, longer treatments associated with a strong selective pressure favour the emergence of resistant clones within commensal organisms. We also emphasise that more studies are needed to identify the optimal duration of antibiotic therapy for common infections, which is important for making changes to the current guidelines, and to identify clinical biomarkers to guide antibiotic treatment in both hospital and ambulatory settings. | 2021 | 33347816 |
| 4228 | 13 | 0.9987 | Resistance to antibiotics in the normal flora of animals. The normal bacterial flora contains antibiotic resistance genes to various degrees, even in individuals with no history of exposure to commercially prepared antibiotics. Several factors seem to increase the number of antibiotic-resistant bacteria in feces. One important factor is the exposure of the intestinal flora to antibacterial drugs. Antibiotics used as feed additives seem to play an important role in the development of antibiotic resistance in normal flora bacteria. The use of avoparcin as a feed additive has demonstrated that an antibiotic considered "safe" is responsible for increased levels of antibiotic resistance in the normal flora enterococci of animals fed with avoparcin and possibly in humans consuming products from these animals. However, other factors like stress from temperature, crowding, and management also seem to contribute to the occurrence of antibiotic resistance in normal flora bacteria. The normal flora of animals has been studied with respect to the development of antibiotic resistance over four decades, but there are few studies with the intestinal flora as the main focus. The results of earlier studies are valuable when focused against the recent understanding of mobile genetics responsible for bacterial antibiotic resistance. New studies should be undertaken to assess whether the development of antibiotic resistance in the normal flora is directly linked to the dramatic increase in antibiotic resistance of bacterial pathogens. Bacteria of the normal flora, often disregarded scientifically, should be studied with the intention of using them as active protection against infectious diseases and thereby contributing to the overall reduction of use of antibioties in both animals and humans. | 2001 | 11432415 |
| 4271 | 14 | 0.9987 | Multi-step vs. single-step resistance evolution under different drugs, pharmacokinetics, and treatment regimens. The success of antimicrobial treatment is threatened by the evolution of drug resistance. Population genetic models are an important tool in mitigating that threat. However, most such models consider resistance emergence via a single mutational step. Here, we assembled experimental evidence that drug resistance evolution follows two patterns: (i) a single mutation, which provides a large resistance benefit, or (ii) multiple mutations, each conferring a small benefit, which combine to yield high-level resistance. Using stochastic modeling, we then investigated the consequences of these two patterns for treatment failure and population diversity under various treatments. We find that resistance evolution is substantially limited if more than two mutations are required and that the extent of this limitation depends on the combination of drug type and pharmacokinetic profile. Further, if multiple mutations are necessary, adaptive treatment, which only suppresses the bacterial population, delays treatment failure due to resistance for a longer time than aggressive treatment, which aims at eradication. | 2021 | 34001313 |
| 9292 | 15 | 0.9987 | Plasmid-free cheater cells commonly evolve during laboratory growth. It has been nearly a century since the isolation and use of penicillin, heralding the discovery of a wide range of different antibiotics. In addition to clinical applications, such antibiotics have been essential laboratory tools, allowing for selection and maintenance of laboratory plasmids that encode cognate resistance genes. However, antibiotic resistance mechanisms can additionally function as public goods. For example, secretion of beta-lactamase from resistant cells, and subsequent degradation of nearby penicillin and related antibiotics, allows neighboring plasmid-free susceptible bacteria to survive antibiotic treatment. How such cooperative mechanisms impact selection of plasmids during experiments in laboratory conditions is poorly understood. Here, we show that the use of plasmid-encoded beta-lactamases leads to significant curing of plasmids in surface grown bacteria. Furthermore, such curing was also evident for aminoglycoside phosphotransferase and tetracycline antiporter resistance mechanisms. Alternatively, antibiotic selection in liquid growth led to more robust plasmid maintenance, although plasmid loss still occurred. The net outcome of such plasmid loss is the generation of a heterogenous population of plasmid-containing and plasmid-free cells, leading to experimental confounds that are not widely appreciated. | 2023 | 37292590 |
| 4272 | 16 | 0.9987 | The hidden impact of antibacterial resistance in respiratory tract infection. Steering an appropriate course: principles to guide antibiotic choice. The prevalence and degree of antibacterial resistance in common respiratory pathogens are increasing worldwide. The health impact of resistance is not yet fully understood. However, once the impact of resistance becomes measurable, it may be too late to apply interventions to reduce resistance levels and regain previous quality and cost of care. We should address resistance now, before patient care is irreversibly compromised. The association between antibiotic consumption and the prevalence of resistance is widely assumed. However, evidence suggests that there is a more complex. multifactorial relationship between antibiotic use and resistance. It is also assumed that there is an adaptive fitness cost for bacterial resistance mutations. However, in some cases, bacteria are able to acquire 'compensatory genes' negating any negative impact of resistance mutations. Mathematical modeling indicates that the timescale for the emergence of resistance is typically shorter than the decay time following a decline in antibiotic consumption. Against this background, a general principle is proposed: to maximize patient outcome whilst minimizing the potential for selection and spread of resistance. This may be achieved through the use of agents that fulfill defined pharmacodynamic and pharmacokinetic parameters and elicit rapid eradication of the bacterial population, including emerging resistant mutants, from the site of infection. The choice of agent may not be the same in all regions, as selection will depend on local resistance patterns and disease etiology; however, the application of this principle may help to preserve the benefits of antibiotic therapy. | 2001 | 11419671 |
| 9436 | 17 | 0.9987 | Phenotypic Resistance to Antibiotics. The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented. | 2013 | 27029301 |
| 4264 | 18 | 0.9987 | Mutational Evolution of Pseudomonas aeruginosa Resistance to Ribosome-Targeting Antibiotics. The present work examines the evolutionary trajectories of replicate Pseudomonas aeruginosa cultures in presence of the ribosome-targeting antibiotics tobramycin and tigecycline. It is known that large number of mutations across different genes - and therefore a large number of potential pathways - may be involved in resistance to any single antibiotic. Thus, evolution toward resistance might, to a large degree, rely on stochasticity, which might preclude the use of predictive strategies for fighting antibiotic resistance. However, the present results show that P. aeruginosa populations evolving in parallel in the presence of antibiotics (either tobramycin or tigecycline) follow a set of trajectories that present common elements. In addition, the pattern of resistance mutations involved include common elements for these two ribosome-targeting antimicrobials. This indicates that mutational evolution toward resistance (and perhaps other properties) is to a certain degree deterministic and, consequently, predictable. These findings are of interest, not just for P. aeruginosa, but in understanding the general rules involved in the evolution of antibiotic resistance also. In addition, the results indicate that bacteria can evolve toward higher levels of resistance to antibiotics against which they are considered to be intrinsically resistant, as tigecycline in the case of P. aeruginosa and that this may confer cross-resistance to other antibiotics of therapeutic value. Our results are particularly relevant in the case of patients under empiric treatment with tigecycline, which frequently suffer P. aeruginosa superinfections. | 2018 | 30405685 |
| 9490 | 19 | 0.9987 | The superbugs: evolution, dissemination and fitness. Since the introduction of antibiotics, bacteria have not only evolved elegant resistance mechanisms to thwart their effect, but have also evolved ways in which to disseminate themselves or their resistance genes to other susceptible bacteria. During the past few years, research has revealed not only how such resistance mechanisms have been able to evolve and to rapidly disseminate, but also how bacteria have, in some cases, been able to adapt to this new burden of resistance with little or no cost to their fitness. Such adaptations make the control of these superbugs all the more difficult. | 1998 | 10066531 |