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J L Martinez – One of the best experts on this subject based on the ideXlab platform.

  • eLS – Antibiotics and the Evolution of Antibiotic Resistance
    Encyclopedia of Life Sciences, 2009
    Co-Authors: J L Martinez, Fernando Baquero

    Abstract:

    Antibiotics were introduced for human therapy few decades ago and their utilization has produced the rapid evolution of bacterial pathogens towards resistance. Before this recent and fast evolution, Antibiotics and their resistance genes have evolved for millions of years in environmental microorganisms. Recent results suggest that, besides serving for inhibiting the growth of competitors, Antibiotics might be signalling molecules in natural ecosystems and that some metabolic enzymes and signal-trafficking efflux pumps might render a phenotype of resistance in the presence of high concentrations of Antibiotics. Antibiotic resistance can be developed by mutation or by the acquisition of resistance determinants by means of horizontal gene transfer. Spread of resistance is achieved through the combination of different elements, from resistance genes to plasmids and bacterial clones. The release of high amounts of Antibiotics and resistance genes in natural habitats is challenging the microbial populations present in these ecosystems.

    Key concepts

    Some Antibiotics can be involved in intermicrobial communication at the low concentrations likely found in most natural ecosystems.

    The origin, spread and diversification of mechanisms of antibiotic resistance is an excellent model for studying real-time evolution.

    The fact that a given gene confers resistance when transferred to a bacterial human pathogen does not necessarily mean that it plays the same functional role in its original host.

    Exaptation is an evolutionary process by which a given determinant changes its function, without changing its structure, as the consequence of an environmental change.

    Anthropogenic antibiotic pollution in the environment might modify the genetic structure of bacterial populations and communities.

    Antibiotic resistance evolves frequently in a modular fashion, combining sequences, genes, genetic platforms and genetic vehicles.

    The association of several antibiotic resistance genes in the same genetic vehicle favours their dissemination and persistence.

    The spread of antibiotic resistance frequently occurs by the global dissemination of particularly transmissible bacterial resistant clones.

    Antibiotic resistance is fixed in human or animal populations when the resistance genes enter into endemic clones.

    Prediction of evolutionary trajectories should constitute the ultimate way to demonstrate the truth of hypothesis in evolutionary sciences.

    Keywords:

    antibiotic resistance;
    horizontal gene transfer;
    bacterial evolution;
    bacterial ecology;
    environmental microbiology;
    mutation rate

  • environmental pollution by Antibiotics and by antibiotic resistance determinants
    Environmental Pollution, 2009
    Co-Authors: J L Martinez

    Abstract:

    Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, Antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain Antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of Antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by Antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations.

  • Towards an ecological approach to Antibiotics and antibiotic resistance genes.
    Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2009
    Co-Authors: A Fajardo, J F Linares, J L Martinez

    Abstract:

    Antibiotics are likely the most important compounds used for human therapy. Conversely, antibiotic resistance is a relevant medical problem. However, besides their relevance for human health, Antibiotics and their resistance genes are important elements that can influence the structure of microbial populations. In this article, we discuss Antibiotics and antibiotic resistance genes in non-clinical environments.

Syma Khalid – One of the best experts on this subject based on the ideXlab platform.

  • Secrets of the Enigmatic Lipid II Revealed by Molecular Dynamics Simulations
    Biophysical Journal, 2017
    Co-Authors: Syma Khalid, Firdaus Samsudin, Timothy S Carpenter, Sarah Witzke

    Abstract:

    Lipid II is critical for the biosynthesis of peptidoglycan; the main component of the bacterial cell wall. Lipid II is targeted by Antibiotics such as the lAntibiotics, which achieve their function by disrupting the biosynthesis of the cell wall. Currently there is an the urgent need for development of novel Antibiotics to counter the growing threat of pathogenic bacteria becoming resistant to currently used Antibiotics. To achieve this, it is imperative we gain a detailed understanding of the molecules targeted by Antibiotics.Relatively little is known about the conformational dynamics of Lipid II, in particular about the unusually long tail. To this end, we present a molecular dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations even within the packed lipidic environment of the membrane. Furthermore we present energetic analysis that reveals the free energy associated with removing Lipid II from the S. aureus membranes compared to other lipids. Thus, we provide unprecedented insights into the conformational dynamics of Lipid II within a Gram-positive bacterial membrane.

  • Molecular Dynamics Simulations Reveal the Conformational Flexibility of Lipid II and Its Loose Association with the Defensin Plectasin in the Staphylococcus aureus Membrane
    Biochemistry, 2016
    Co-Authors: Sarah Witzke, Timothy S Carpenter, Michael B. Petersen, Syma Khalid

    Abstract:

    Lipid II is critical for peptidoglycan synthesis, which is the main component of the bacterial cell wall. Lipid II is a relatively conserved and important part of the cell wall biosynthesis pathway and is targeted by Antibiotics such as the lAntibiotics, which achieve their function by disrupting the biosynthesis of the cell wall. Given the urgent need for development of novel Antibiotics to counter the growing threat of bacterial infection resistance, it is imperative that a thorough molecular-level characterization of the molecules targeted by Antibiotics be achieved. To this end, we present a molecular dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational l…

Sarah Witzke – One of the best experts on this subject based on the ideXlab platform.

  • Secrets of the Enigmatic Lipid II Revealed by Molecular Dynamics Simulations
    Biophysical Journal, 2017
    Co-Authors: Syma Khalid, Firdaus Samsudin, Timothy S Carpenter, Sarah Witzke

    Abstract:

    Lipid II is critical for the biosynthesis of peptidoglycan; the main component of the bacterial cell wall. Lipid II is targeted by Antibiotics such as the lAntibiotics, which achieve their function by disrupting the biosynthesis of the cell wall. Currently there is an the urgent need for development of novel Antibiotics to counter the growing threat of pathogenic bacteria becoming resistant to currently used Antibiotics. To achieve this, it is imperative we gain a detailed understanding of the molecules targeted by Antibiotics.Relatively little is known about the conformational dynamics of Lipid II, in particular about the unusually long tail. To this end, we present a molecular dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations even within the packed lipidic environment of the membrane. Furthermore we present energetic analysis that reveals the free energy associated with removing Lipid II from the S. aureus membranes compared to other lipids. Thus, we provide unprecedented insights into the conformational dynamics of Lipid II within a Gram-positive bacterial membrane.

  • Molecular Dynamics Simulations Reveal the Conformational Flexibility of Lipid II and Its Loose Association with the Defensin Plectasin in the Staphylococcus aureus Membrane
    Biochemistry, 2016
    Co-Authors: Sarah Witzke, Timothy S Carpenter, Michael B. Petersen, Syma Khalid

    Abstract:

    Lipid II is critical for peptidoglycan synthesis, which is the main component of the bacterial cell wall. Lipid II is a relatively conserved and important part of the cell wall biosynthesis pathway and is targeted by Antibiotics such as the lAntibiotics, which achieve their function by disrupting the biosynthesis of the cell wall. Given the urgent need for development of novel Antibiotics to counter the growing threat of bacterial infection resistance, it is imperative that a thorough molecular-level characterization of the molecules targeted by Antibiotics be achieved. To this end, we present a molecular dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational l…