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Journal ArticleDOI

Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?

01 Mar 2005-Nature Reviews Microbiology (Springer Science and Business Media LLC)-Vol. 3, Iss: 3, pp 238-250
TL;DR: In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented and several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibits protein synthesis or inhibit enzymatic activity.
Abstract: Antimicrobial peptides are an abundant and diverse group of molecules that are produced by many tissues and cell types in a variety of invertebrate, plant and animal species. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of antimicrobial peptide activity, their relevance to how peptides damage and kill microorganisms still need to be clarified. Recently, there has been speculation that transmembrane pore formation is not the only mechanism of microbial killing. In fact several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity. In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented.
Citations
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Journal ArticleDOI
TL;DR: This review details the significant advances that have been made in understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.
Abstract: Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.

2,915 citations


Cites background from "Antimicrobial peptides: pore former..."

  • ...Justifiably, significant attention is being directed toward eukaryotic antimicrobial peptides, which are ubiquitous elements of the innate immune response in a variety of invertebrate, plant, and animal species (64)....

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Journal ArticleDOI
TL;DR: The major strategies for designing surfaces that prevent fouling due to proteins, bacteria, and marine organisms are reviewed and ongoing research in this area should result in the development of even better antifouling materials in the future.
Abstract: The major strategies for designing surfaces that prevent fouling due to proteins, bacteria, and marine organisms are reviewed. Biofouling is of great concern in numerous applications ranging from biosensors to biomedical implants and devices, and from food packaging to industrial and marine equipment. The two major approaches to combat surface fouling are based on either preventing biofoulants from attaching or degrading them. One of the key strategies for imparting adhesion resistance involves the functionalization of surfaces with poly(ethylene glycol) (PEG) or oligo(ethylene glycol). Several alternatives to PEG-based coatings have also been designed over the past decade. While protein-resistant coatings may also resist bacterial attachment and subsequent biofilm formation, in order to overcome the fouling-mediated risk of bacterial infection it is highly desirable to design coatings that are bactericidal. Traditional techniques involve the design of coatings that release biocidal agents, including antibiotics, quaternary ammonium salts (QAS), and silver, into the surrounding aqueous environment. However, the emergence of antibiotic- and silver-resistant pathogenic strains has necessitated the development of alternative strategies. Therefore, other techniques based on the use of polycations, enzymes, nanomaterials, and photoactive agents are being investigated. With regard to marine antifouling coatings, restrictions on the use of biocide-releasing coatings have made the generation of nontoxic antifouling surfaces more important. While considerable progress has been made in the design of antifouling coatings, ongoing research in this area should result in the development of even better antifouling materials in the future.

2,278 citations

Journal ArticleDOI
TL;DR: The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides.
Abstract: Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.

2,231 citations


Cites background from "Antimicrobial peptides: pore former..."

  • ...acid synthesis, protein synthesis, enzymatic activity, and cell wall synthesis (28) (Fig....

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Journal ArticleDOI
TL;DR: How environmental factors, infectious microbes, ethnic origin, genetic susceptibility, and a dysregulated immune system can result in mucosal inflammation are discussed.

1,749 citations

Journal ArticleDOI
TL;DR: In this article, advanced computer assisted design strategies that address the difficult problem of relating primary sequence to peptide structure, and are delivering more potent, cost-effective, broad-spectrum peptides as potential next-generation antibiotics.
Abstract: Multidrug-resistant bacteria are a severe threat to public health. Conventional antibiotics are becoming increasingly ineffective as a result of resistance, and it is imperative to find new antibacterial strategies. Natural antimicrobials, known as host defence peptides or antimicrobial peptides, defend host organisms against microbes but most have modest direct antibiotic activity. Enhanced variants have been developed using straightforward design and optimization strategies and are being tested clinically. Here, we describe advanced computer-assisted design strategies that address the difficult problem of relating primary sequence to peptide structure, and are delivering more potent, cost-effective, broad-spectrum peptides as potential next-generation antibiotics.

1,543 citations


Cites background from "Antimicrobial peptides: pore former..."

  • ...In vitro studies have revealed that direct antimicrobial activity is not limited to the previously suggested mechanisms of membrane and/or cell rupture but instead extends to interference with membrane-associated biosynthesis, macromolecular synthesis in the cytoplasm and metabolic function...

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References
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Journal ArticleDOI
TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.
Abstract: The MOLSCRIPT program produces plots of protein structures using several different kinds of representations. Schematic drawings, simple wire models, ball-and-stick models, CPK models and text labels can be mixed freely. The schematic drawings are shaded to improve the illusion of three dimensionality. A number of parameters affecting various aspects of the objects drawn can be changed by the user. The output from the program is in PostScript format.

13,971 citations

Journal ArticleDOI
21 May 1999-Science
TL;DR: Improvements in understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
Abstract: Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.

11,162 citations


"Antimicrobial peptides: pore former..." refers background in this paper

  • ...This includes the concentrations of antimicrobial peptides at the sites of infection, the role of synergistic substances that might be present in tissues and fluids (for example, the presence of lysozyme, other antimicrobial peptides and proteins, and the absence of divalent cations), the role of inhibiting substances that might be present (for example, physiological concentrations of salts and serous proteins) and the unusual characteristics of bacteria replicating in vivo , particularly those in biofilm...

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Journal ArticleDOI
24 Jan 2002-Nature
TL;DR: As the need for new antibiotics becomes more pressing, could the design of anti-infective drugs based on the design principles these molecules teach us?
Abstract: Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?

7,657 citations

Book ChapterDOI
TL;DR: Raster3D is discussed, which is a suite of programs for molecular graphics, which must compromise the quality of rendered images to achieve rendering speeds high enough for useful interactive manipulation of three-dimensional objects.
Abstract: Publisher Summary This chapter discusses Raster3D, which is a suite of programs for molecular graphics. Crystallographers were among the first and most avid consumers of graphics workstations. Rapid advances in computer hardware, and particularly in the power of specialized computer graphics boards, have led to successive generations of personal workstations with ever more impressive capabilities for interactive molecular graphics. For many years, it was standard practice in crystallography laboratories to prepare figures by photographing directly from the workstation screen. No matter how beautiful the image on the screen, however, this approach suffers from several intrinsic limitations. Among these is the inherent limitation imposed by the effective resolution of the screen. Use of the graphics hardware in a workstation to generate images for later presentation can also impose other limitations. Designers of workstation hardware must compromise the quality of rendered images to achieve rendering speeds high enough for useful interactive manipulation of three-dimensional objects.

3,735 citations

Journal ArticleDOI
TL;DR: This review, inspired by a spate of recent studies ofdefensins in human diseases and animal models, focuses on the biological function of defensins.
Abstract: The production of natural antibiotic peptides has emerged as an important mechanism of innate immunity in plants and animals. Defensins are diverse members of a large family of antimicrobial peptides, contributing to the antimicrobial action of granulocytes, mucosal host defence in the small intestine and epithelial host defence in the skin and elsewhere. This review, inspired by a spate of recent studies of defensins in human diseases and animal models, focuses on the biological function of defensins.

2,718 citations