Antibiotics

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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.

  • Antibiotics and antibiotic resistance genes in natural environments
    Science, 2008
    Co-Authors: J L Martinez
    Abstract:

    The large majority of Antibiotics currently used for treating infections and the antibiotic resistance genes acquired by human pathogens each have an environmental origin. Recent work indicates that the function of these elements in their environmental reservoirs may be very distinct from the "weapon-shield" role they play in clinical settings. Changes in natural ecosystems, including the release of large amounts of antimicrobials, might alter the population dynamics of microorganisms, including selection of resistance, with consequences for human health that are difficult to predict.

  • Antibiotics and antibiotic resistance in water environments
    Current Opinion in Biotechnology, 2008
    Co-Authors: Fernando Baquero, J L Martinez, Rafael Canton
    Abstract:

    Antibiotic-resistant organisms enter into water environments from human and animal sources. These bacteria are able to spread their genes into water-indigenous microbes, which also contain resistance genes. On the contrary, many Antibiotics from industrial origin circulate in water environments, potentially altering microbial ecosystems. Risk assessment protocols for Antibiotics and resistant bacteria in water, based on better systems for Antibiotics detection and antibiotic-resistance microbial source tracking, are starting to be discussed. Methods to reduce resistant bacterial load in wastewaters, and the amount of antimicrobial agents, in most cases originated in hospitals and farms, include optimization of disinfection procedures and management of wastewater and manure. A policy for preventing mixing human-originated and animal-originated bacteria with environmental organisms seems advisable.

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...

Marc J. M. Bonten - One of the best experts on this subject based on the ideXlab platform.

  • Handling time dependent variables: Antibiotics and antibiotic resistance
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016
    Co-Authors: L. Silvia Munoz-price, Jos F. Frencken, Sergey Tarima, Marc J. M. Bonten
    Abstract:

    Elucidating quantitative associations between antibiotic exposure and antibiotic resistance development is important. In the absence of randomized trials, observational studies are the next best alternative to derive such estimates. Yet, as Antibiotics are prescribed for varying time periods, Antibiotics constitute time-dependent exposures. Cox regression models are suited for determining such associations. After explaining the concepts of hazard, hazard ratio, and proportional hazards, the effects of treating antibiotic exposure as fixed or time-dependent variables are illustrated and discussed. Wider acceptance of these techniques will improve quantification of the effects of Antibiotics on antibiotic resistance development and provide better evidence for guideline recommendations.

  • Fighting antibiotic resistance in the intensive care unit using Antibiotics
    Future microbiology, 2015
    Co-Authors: Nienke L. Plantinga, Bastiaan H J Wittekamp, Pleun Joppe Van Duijn, Marc J. M. Bonten
    Abstract:

    Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with Antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

Craig D Adams - One of the best experts on this subject based on the ideXlab platform.

  • Treatment of Antibiotics and antibiotic resistant bacteria in swine wastewater with free chlorine
    Journal of Agricultural and Food Chemistry, 2006
    Co-Authors: Zhimin Qiang, John J. Macauley, Rao Surampalli, Melanie R. Mormile, Craig D Adams
    Abstract:

    Recent recognition of the occurrence of Antibiotics in the environment has highlighted concerns regarding potential threats of Antibiotics to humans and wildlife. Antibiotics are commonly applied to animals to prevent diseases and promote growth, making livestock agriculture a major source of antibiotic pollution. The purpose of our study was to examine chlorination technology as a method for preventing the release of Antibiotics as well as antibiotic-resistant bacteria into the environment from concentrated animal feeding operations. Wastewaters from various sites of two anaerobic lagoon systems, one aerated and the other not, on a swine facility were investigated. Each system consisted of a primary treatment lagoon and a subsequent polishing lagoon. Free chlorine (or monochloramine for comparison) was applied to oxidize Antibiotics and to disinfect lagoon bacteria as well. Results indicate that aeration substantially improves lagoon functionality, thereby adding both organic and ammonia removal. Ammonia present in the wastewaters plays a critical role in Antibiotics decomposition and bacterial inactivation due to its rapid competition for free chlorine to form monochloramine. Generally, a chlorine dose close to breakpoint is required to achieve complete removal of Antibiotics, leading to high consumption of free chlorine in most of the wastewaters examined. However, because of a low ammonia concentration in the polishing lagoon wastewater of the aerated system, a chlorine dose of 100 mg/L can effectively achieve complete removal of both Antibiotics and bacteria. On the basis of our experimental findings, a possible strategy for the treatment of swine wastewater is suggested.