Evolution Of Resistance In Bacteria Research Articles

Antibiotic Resistance: Do We Need Only Cutting-Edge Methods, or Can New Visions Such as One Health Be More Useful for Learning from Nature?

Antibiotic resistance is an increasing global problem for public health, and focusing on biofilms has provided further insights into resistance evolution in bacteria. Resistance is innate in many bacterial species, and many antibiotics are derived from natural molecules of soil microorganisms. Is it possible that nature can help control AMR diffusion? In this review, an analysis of resistance mechanisms is summarized, and an excursus of the different approaches to challenging resistance spread based on natural processes is presented as "lessons from Nature". On the "host side", immunotherapy strategies for bacterial infections have a long history before antibiotics, but continuous new inputs through biotechnology advances are enlarging their applications, efficacy, and safety. Antimicrobial peptides and monoclonal antibodies are considered for controlling antibiotic resistance. Understanding the biology of natural predators is providing new, effective, and safe ways to combat resistant bacteria. As natural enemies, bacteriophages were used to treat severe infections before the discovery of antibiotics, marginalized during the antibiotic era, and revitalized upon the diffusion of multi-resistance. Finally, sociopolitical aspects such as education, global action, and climate change are also considered as important tools for tackling antibiotic resistance from the One Health perspective.

Driven Disordered Systems Approach to Biological Evolution in Changing Environments

Biological evolution of a population is governed by the fitness landscape, which is a map from genotype to fitness. However, a fitness landscape depends on the organism's environment, and evolution in changing environments is still poorly understood. We study a particular model of antibiotic resistance evolution in bacteria where the antibiotic concentration is an environmental parameter and the fitness landscapes incorporate tradeoffs between adaptation to low and high antibiotic concentration. With evolutionary dynamics that follow fitness gradients, the evolution of the system under slowly changing antibiotic concentration resembles the athermal dynamics of disordered physical systems under quasistatic external drives. Specifically, our model can be described as a system with interacting hysteretic elements, and it exhibits effects such as hysteresis loops and memory formation under antibiotic concentration cycling. Using methods familiar from studies in this field, we derive a number of analytical and numerical results. Our approach provides a general framework for studying motifs of evolutionary dynamics in biological systems in a changing environment.

Antibiotic susceptibility pattern of bacterial strains isolated from different clinical samples in Multan, Pakistan

Rapid evolution of resistance in bacteria towards antibiotics has dramatically become a global health crisis. The aim of present study was to check the prevalence and antimicrobial sensitivity of bacteria present in clinical samples. Two hundred and seventy different clinical samples were examined in laboratory of the Chaudhary Pervaiz Elahi Institute of Cardiology, Multan Pakistan. Clinical isolates were isolated on MacConkey agar, blood agar and Cystine Lactose Electrolyte Deficient Agar (CLED Agar). The isolated strains were tested for antimicrobial susceptibility against the panel of 27 antibiotics. Out of 270 sample, 91(33.7%) showed microbial load. Staphylococcus aureus, Pseudomonas spp., Escherichia coli, Klebsiella spp. and Candida spp. were commonly isolated. Staphylococcus aureus showed the highest prevalence as monoresistant and polyresistant strain. The malpractice of self-medication with unrestricted supply of medicines have played an important role in antimicrobial resistance. Keywords: Antimicrobial resistance; Escherichia coli; ESBL; Zone of inhibition http://dx.doi.org/10.19045/bspab.2020.90232

Phage-antibiotic combinations: a promising approach to constrain resistance evolution in bacteria.

Antibiotic resistance has reached dangerously high levels throughout the world. A growing number of bacteria pose an urgent, serious, and concerning threat to public health. Few new antibiotics are available to clinicians and only few are in development, highlighting the need for new strategies to overcome the antibiotic resistance crisis. Combining existing antibiotics with phages, viruses the infect bacteria, is an attractive and promising alternative to standalone therapies. Phage-antibiotic combinations have been shown to suppress the emergence of resistance in bacteria, and sometimes even reverse it. Here, we discuss the mechanisms by which phage-antibiotic combinations reduce resistance evolution, and the potential limitations these mechanisms have in steering microbial resistance evolution in a desirable direction. We also emphasize the importance of gaining a better understanding of mechanisms behind physiological and evolutionary phage-antibiotic interactions in complex in-patient environments.

Role of a Concentration Gradient in Malaria Drug Resistance Evolution: A Combined within- and between-Hosts Modelling Approach

Resistance to antimalarial drugs is currently a growing public health problem, resulting in more cases with treatment failure. Although previous studies suggested that a concentration gradient facilitates the antibiotic resistance evolution in bacteria, no attempt has been made to investigate the roles of a concentration gradient in malaria drug resistance. Unlike the person-to-person mode of transmission of bacteria, the malaria parasites need to switch back and forth between the human and mosquito hosts to complete the life cycle and to spread the resistant alleles. Here we developed a stochastic combined within- and between-hosts evolutionary dynamics model specific to malaria parasites in order to investigate the influence of an antimalarial concentration gradient on the evolutionary dynamics of malaria drug resistance. Every stage of malaria development in both human and mosquito hosts are individually modelled using the tau-leaping algorithm. We found that the concentration gradient can accelerate antimalarial resistance evolution. The gain in resistance evolution was improved by the increase in the parasite mutation rate and the mosquito biting rate. In addition, even though the rate of resistance evolution is not sensitive to the changes in parasite reduction ratios (PRRs) of antimalarial drugs, the probability of finding the antimalarial drug resistant parasites decreases when the PRR increases.

Within-host dynamics shape antibiotic resistance in commensal bacteria.

The spread of antibiotic resistance, a major threat to human health, is poorly understood. Simple population-level models of disease transmission predict that above a certain rate of antibiotic consumption in a population, resistant bacteria should completely eliminate non-resistant strains, while below this threshold they should be unable to persist at all. This prediction stands at odds with empirical evidence showing that resistant and non-resistant strains coexist stably over a wide range of antibiotic consumption rates. Not knowing what drives this long-term coexistence is a barrier to developing evidence-based strategies for managing the spread of resistance. Here, we argue that competition between resistant and sensitive pathogens within individual hosts gives resistant pathogens a relative fitness benefit when they are rare, promoting coexistence between strains at the population level. To test this hypothesis, we embed mechanistically-explicit within-host dynamics in a structurally-neutral disease transmission model. Doing so allows us to reproduce patterns of resistance observed in the opportunistic pathogens Escherichia coli and Streptococcus pneumoniae across European countries, and to identify factors that may shape resistance evolution in bacteria by modulating the intensity and outcomes of within-host competition.

Molecular Mechanism of Antibiotic Resistance: The Untouched Area of Future Hope.

The treatment of bacterial infections is becoming increasingly ineffective due to rapid mutation which leads to antibiotic resistant and resistant bacteria become more prevalent. As a result the existing antibiotics are gradually obsolete and again new drugs are needed to be designed for the same threat. However, the prediction of evolutionary processes/antibiotic resistance is uncertain. Still, the understanding of mode of evolution of resistance in bacteria is a determining step in the preclinical development of new antibiotics, because drug developers assess the risk of resistance arising against a drug during preclinical development. Multidrug efflux pump systems play an important role for making multidrug resistance to a range of clinically important antibiotics in gram-negative bacteria like Pseudomonas aeruginosa, which lower the intracellular drug concentration by exporting incoming antibiotics across the membranes. We tried to show that the wild type susceptible bacteria P. aeruginosa modified its genetic makeup at mutational hotspots under stress. This strain may either become multidrug resistant or remain susceptible depending on position of amino acid changes in regulatory proteins of efflux pump. Multidrug resistant strain made significant changes at the amino acid positions, 103rd (G → A) and 126th (E → V) through the mutation on the nucleotide position of 308th (G → C); both 377th (A → T) and 378th (G → T), respectively in mexR, a repressor of mexAB-oprM efflux pump. This mutant protein showed low affinity with their operator. But the alteration at 103th position (G → A) in mexR may provide almost similar structural and functional stability as wild type. It was found that mutation was seemed to be well regulated within the limit and position specific under stress which might be back to its original form by supplying counter stress unless addition or deletion takes place.

Phage Therapy Faces Evolutionary Challenges.

Antibiotic resistance evolution in bacteria indicates that one of the challenges faced by phage therapy is that, sooner or later, bacteria will evolve resistance to phages. Evidently, this is the case of every known antimicrobial therapy, but here this is also part of a ubiquitous natural process of co-evolution between phages and bacteria. Fundamental evolutionary studies hold some clues that are crucial to limit the problematic process of bacterial resistance during phage applications. First, I discuss here the importance of defining evolutionary and ecological factors influencing bacterial resistance and phage counter-defense mechanisms. Then, I comment on the interest of determining the co-evolutionary dynamics between phages and bacteria that may allow for selecting the conditions that will increase the probability of therapeutic success. I go on to suggest the varied strategies that may ensure the long-term success of phage therapy, including analysis of internal phage parameters and personalized treatments. In practical terms, these types of approaches will define evolutionary criteria regarding how to develop, and when to apply, therapeutic phage cocktails. Integrating this perspective in antimicrobial treatments, such as phage therapy, is among the necessary steps to expand its use in the near future, and to ensure its durability and success.

Evolution of drug resistance in bacteria

Evolution of drug resistance in bacteria

ESCAPING AN EVOLUTIONARY LOBSTER TRAP: DRUG RESISTANCE AND COMPENSATORY MUTATION IN A FLUCTUATING ENVIRONMENT

The fitness landscape concept aids intuition on adaptive evolution through low fitness genotypes. Evolutionary processes become complex when environments and therefore fitnesses fluctuate. Antibiotic resistance evolution in bacteria is an important example of such dynamics. Resistance bears a cost in the drug-free environment, but compensatory mutation can lower this cost, creating a fitness valley. With the drug present, the valley becomes a hill that is easily climbed. Once a population is dominated by resistant-compensated genotypes, reversion to sensitivity is difficult: this phenomenon has been described as an evolutionary lobster trap. With increasing frequencies of drug resistance among pathogenic bacteria, it is critical to understand how this trap can be escaped. Here, we develop stochastic models to investigate these dynamics. The residual fitness cost (the cost remaining after compensatory mutation has occurred) is a key parameter. Reversion to sensitivity is favored when the time spent in the absence of the drug relative to its presence is high compared to the residual fitness cost. Population sizes are also important: in large populations, resistant-compensated mutants appear in resistant-uncompensated or sensitive-compensated genotypes without fixation of these intermediates. This stochastic tunneling effect occurs when sufficient time is allowed by the rates of environmental fluctuation.

Parasite Evolution and Life History Theory

Parasite Evolution and Life History Theory

Mice Are Not Furry Petri Dishes

The evolution of drug resistance in bacteria depends on a rapid mutation rate. However, drug resistance mutations frequently incur a cost to the microbe, usually a reduced growth rate. Unfortunately, this cost cannot be exploited because those crafty microbes usually develop compensatory mutations, which offset the growth disadvantage while maintaining drug resistance. In a Perspective, Bull and Levin discuss new findings ( BjA¶rkman et al. ) showing that different compensatory mutations evolve depending on whether pathogenic bacteria are grown in culture or in an animal host. They caution that care should be taken when trying to extrapolate in vitro findings about bacterial drug resistance to in vivo situations.

Characterization of new resistance plasmids belonging to incompatibility group IncQ.

New IncQ R plasmids, pIE639 and pIE723, are characterized and compared to the prototype IncQ plasmid RSF1010. Additional resistance determinants not common on other R plasmids are located on small stretches of DNA interspacing essential regions at different positions in an otherwise unchanged core of IncQ plasmid DNA. The contribution of IncQ plasmids to resistance evolution in bacteria is discussed.