Glycopeptide Antibiotics

10 Key excerpts on "Glycopeptide Antibiotics"

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  Biochemistry of Peptide Antibiotics

  Recent Advances in the Biotechnology of ß-Lactams and Microbial Bioactive Peptides

  • Horst Kleinkauf, Hans von Döhren(Authors)
  • 2019(Publication Date)
  • De Gruyter

    (Publisher)

  Chapter 7 Glycopeptide Antibiotics of the Vancomycin Group G. C. Lancini and B. Cavalieri 1. Introduction 2. Producing Organisms 3. Chemistry 4. Biosynthesis 5. Mechanism of Action 5.1 Effect on growing cultures 5.2 Studies with cell free systems 5.3 Action at molecular level 6. Relation of Antimicrobial Activity and Mechanism of Action References 1. Introduction Vancomycin [1], an antibiotic effective in the treatment of severe Gram-positive infections, was isolated in 1956 from cultures of Streptomyces orientalis [2]. Al-though its chemical structure was completely elucidated only several years later [3, 4], it was soon recognized as the first member of a new family of antibiotics known at present as Glycopeptide Antibiotics or more precisely Glycopeptide Antibiotics of the vancomycin group. The common characteristics of these products are easily defined on the basis of chemical structure and biological properties. From the chemical point of view they are linear heptapeptides in which at least five of the amino acid residues are benzenic rings linked each other to form a triphenylether moiety and a diphenyl group. The aromatic rings may carry various substituents as hydroxy or methyl groups, sugars, chlorine atoms. From the biological point of view the most striking feature is their mechanism of action. In fact, they inhibit the growth of sensitive bacteria by binding to the D-alanyl-D-alanine terminus of one or more intermediates of the cell wall synthesis, thus determining the cell disruption [5, 6], Although initially scanty used vancomycin became more and more clinically im-portant because of its activity on staphylococci resistant to the /¡-lactams and other commonly used antibiotics [1]. This spurred the research of new members of this 1 6 0 G l y c o p e p t i d e A n t i b i o t i c s o f t h e V a n c o m y c i n G r o u p o O s u o . _ I » -3 8 ° 1 .2 2 u Q Crt ^ D O J3 '-3 .ti H . 2 E _ XI 52 o -a .2; t i .

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  Biocatalysis

  Biochemical Fundamentals and Applications

  • Peter Grunwald(Author)
  • 2017(Publication Date)
  • WSPC (EUROPE)

    (Publisher)

  Chapter 8

  Synthesis of Peptide Antibiotics

  The various known antibiotics (Greek: anti ‘against’, bios ‘live’) act in rather different ways either on eukaryotes, on prokaryotes, or on both. e They may inhibit RNA-polymerase (transcription), bind to the ribosomal subunits, and hamper protein biosynthesis, or inhibit the binding of an aminoacyl t-RNA to the ribosome. Puromycin, a nucleoside antibiotic from Streptomyces alboniger, is an example of an antibiotic that can be incorporated into the growing peptide chain, leading to its termination (Chapter 15 ). Antimycins as Antimycin A2 (they all have a 9-membered ring with two lactone groups in common) isolated from a Streptomyces strain provoke decoupling of the oxidative phosphorylation from the respiratory chain. Hence, many antibiotics are extremely toxic for mammals, and antibiotics employed for clinical application are not free from side effects, too. On the other hand, one reason for remaining healthy is that all living organisms including plants synthesize a set of antimicrobial peptides (e.g., defensins etc.) composed of 15 to 47 amino acid residues with a positive net charge, constituting the main components of ‘innate immunity’ (Boman, 2003).

  8.1 Antibiotics — Some General Aspects

  Microorganisms like bacteria and fungi possess secondary metabolic pathways for the production of a multitude of different compounds among them peptides with a high diversity in respect of rather complex structures and biological activities. Within the fungal kingdom, filamentous ones are especially productive sources for biologically active secondary metabolites due to their greater metabolic complexity compared to yeasts. Antibacterial peptides often display cyclic structures. The cyclic structure influences their physical properties; among the most important is solubility which is very low in water (due to the fact that the oxygen atoms are oriented towards the inner of the molecules) but high in lipids. Prevalently, such peptides — also called ionophores — act by impairing the lipid bilayer of cell membranes through forming pores. This makes it impossible to maintain electrochemical gradients across the cell membrane, prevents ATP-synthesis, and may in addition cause a loss of ions as well as an influx of water, associated with an osmolysis of the cell. Neutral ionophores as valinomycin, a cyclic depsipeptide occurring in Streptomyces fulvissimus containing L -valine, D -valine, D -α-hydroxy-isovaleric acid and lactic acid in its 36-membered ring form complexes with cations and thus migrate only to the direction of the negative side of the membrane. Negatively charged ionophores become neutral by complex formation with cations. They can cross the membrane in each direction. An example is nigericin that is capable of discharging the ion gradient of a cell membrane (Dolowny, 2001 and literature cited there). From the medical point of view an interruption of the synthesis of special compounds that are essential for the survival of a pathogenic microorganism are of high importance. Prominent examples are yersiniabactin or mycobactin. Both peptides bind metal ions as Fe3+ with high affinity and are responsible for the Fe2+ -supply of their producers which are yersinia pestis, and mycobacterium tuberculosus (Wandersman et al., 2004; Dürfahrt and Marahiel, 2005). Another iron chelator is the small molecule vibriobactin biosynthesized by Vibrio cholerae

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  Glycopeptide Antibiotics

  • Ramakris Nagarajan(Author)
  • 2020(Publication Date)
  • CRC Press

    (Publisher)

  1

  Glycopeptides

  Classification, Occurrence, and Discovery

  RAYMOND C. YAO and LOUISE W. CRANDALL Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana

  I. Introduction

  A. Historical Aspect

  Vancomycin was first discovered at Eli Lilly and Company in a natural products screening program in the early 1950s directed at new antibiotic-producing microorganisms (1). This antibiotic, active primarily against Gram-positive bacteria, was produced by a new species of actinomycete isolated from an Indonesian soil; subsequently, two other vancomycin-producing strains were isolated from samples of Indian soil (2). The culture, originally designated Streptomyces orientalis , was later renamed Nocardia orientalis based on the tendency of the vegetative hyphae to break into small, squarish units often referred to as “fragments” (3). With the advent of chemotaxonomic techniques that include the analysis of cell wall amino acids and sugars, whole-cell sugars, fatty acids (including mycolic acids), mena-quinones, and phospholipids, this nocardioform, which lacks mycolic acids, was eventually reclassified as Amycolatopsis orientalis (4).

  The discovery of vancomycin was followed a year later by the isolation of ristocetin (5). These two antibiotics were recognized as belonging to a chemical class of antibiotics called glycopeptides, but their complete structures were not determined until some years later. The glycopeptides are complex molecules, characterized by a multiring peptide core containing six peptide linkages, an unusual triphenyl ether moiety, and sugars attached at various sites. Over 30 antibiotics designated as belonging to the glycopeptide class have been reported. As is expected with microbial secondary metabolites, most of these antibiotics have first been isolated as families of closely related factors.

  B. Medical and Agricultural Uses

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  Bacterial Resistance to Antibiotics

  From Molecules to Man

  • Boyan B. Bonev, Nicholas M. Brown, Boyan B. Bonev, Nicholas M. Brown(Authors)
  • 2019(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  3 Resistance to Glycopeptide Antibiotics

  François Lebreton

  1

  and Vincent Cattoir

  2,3,4

  1

  Departments of Ophthalmology, Microbiology and Immunobiology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA

  2

  Inserm Unit U1230, University of Rennes 1, Rennes, France

  3

  Department of Clinical Microbiology, Rennes University Hospital, Rennes, France

  4

  National Reference Center for Antimicrobial Resistance (Lab Enterococci), Rennes, France

  3.1 Introduction

  Antibiotics of the glycopeptide family share closely related chemical structures and are naturally obtained from various species of actinomycetes, typically recovered from soil samples [1] . All glycopeptides exhibit a narrow spectrum of activity, being active only against aerobic and anaerobic Gram‐positive bacteria. Of note, only vancomycin and teicoplanin are clinically used in the treatment of severe infections caused by resistant Gram‐positive pathogens, especially

  methicillin‐resistant Staphylococcus aureu

  s (MRSA ) and enterococci, or for patients with an allergy to β‐lactam antibiotics. In addition, vancomycin is recommended for the treatment of severe and complicated infections caused by Clostridium difficile [2] . As opposed to vancomycin that was approved for use by the FDA in 1958 and then used worldwide, teicoplanin is not available in the United States but is used in Europe [3] . Teicoplanin presents some advantages over vancomycin because it presents a lower toxicity, a better tissue penetration, and a prolonged serum half‐life [4] .

  Structurally related to natural glycopeptides, three semisynthetic lipoglycopeptides (i.e., dalbavancin, oritavancin, and telavancin) have been recently developed for the treatment of infections caused by resistant Gram‐positive pathogens. Of them, only telavancin is currently approved for the treatment of patients with complicated skin and soft‐tissue infections (USA and Canada) or hospital‐acquired pneumonia, including ventilator‐associated pneumonia, caused by MRSA [5 , 6 ]. Like teicoplanin, telavancin seems to be less toxic than vancomycin with a prolonged half‐life allowing for a once‐daily dosing [7]

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  Food Biotechnology

  • Anthony Pometto, Kalidas Shetty, Gopinadhan Paliyath, Robert E. Levin(Authors)
  • 2005(Publication Date)
  • CRC Press

    (Publisher)

  These proteinaceous molecules often contain novel amino acid configurations and modifications when compared to normal ribosomally synthesized poly-peptides (2). These compounds are typically broken up into two groups, the bacteriocins, and the peptide antibiotics, based upon their biosynthetic mechanisms. Bacteriocins are ribosomally synthesized compounds produced by bacteria that are active against closely related bacteria (3). Most bacteriocins consist of 20–60 amino acids that may or may not undergo post translational modifications. As hydrophobic or amphi-philic compounds, most bacteriocins target cell membranes, while some also inhibit the biosynthesis of biopolymers (e.g., some colicins), or enzyme activities (e.g., duramycin). The peptide antibiotics are nonribosomally synthesized and instead are formed through complex, stepwise condensation reactions that utilize large, nonribosomal peptide synthetases (NRPS) (4,5). These compounds often have nonprotein amino acids, including D-amino acids, hydroxy acids, or other unusual constituents and demonstrate a broad range of inhibition mechanisms and spectrums of activity (6). Here, we will organize our coverage of the antimicrobial peptides into a slightly dif-ferent scheme according to their applicability to the food industry, placing emphasis on those classes of compounds which are either applicable in foods or whose knowledge base provides insights into food applicable compounds. We will then review some of the current industrial applications of the antimicrobial peptides, and provide some insights into the exciting future prospectus of the field. 7.2 GRAM-POSITIVE BACTERIOCINS Due to their natural occurrence in many types of foods, numerous Gram-positive bacteria species are considered to have food grade, or Generally Regarded as Safe (GRAS), status. Gram-positive bacteria produce a variety of bacteriocins, many of which have been bio-chemically and genetically characterized.

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  Antibiotic Drug Resistance

  • José-Luis Capelo-Martínez, Gilberto Igrejas, José-Luis Capelo-Martínez, Gilberto Igrejas(Authors)
  • 2019(Publication Date)
  • Wiley

    (Publisher)

  Part I Current Antibiotics and Their Mechanism of Action Passage contains an image

  1 Resistance to Aminoglycosides : Glycomics and the Link to the Human Gut Microbiome

  Viviana G. Correia Benedita A. Pinheiro Ana Luísa Carvalho, and Angelina S. Palma

  UCIBIO‐REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Caparica, Portugal

  1.1 Aminoglycosides as Antimicrobial Drugs

  The exponential appearance of antibiotic‐resistant infections, in particular those caused by Gram‐negative pathogens, is a major public health concern. The observed decrease in the emergence of new effective antimicrobial drugs is an inevitable consequence of the use of antibiotics, and new approaches to fight infection are a matter in need of attention from the scientific community (Magiorakos et al. 2012 ). In response to this challenge, the optimization of existing drugs with known mechanisms of action and resistance, such as aminoglycosides, is an attractive approach for the development of new antimicrobials.

  Aminoglycosides or aminoglycoside antibiotics (AGAs) are secondary metabolites of bacteria used in the warfare against other microorganisms, which were repurposed in medicine as broad‐spectrum antibiotics in both humans and animals. This class of antibiotics has activity against Gram‐negative and Gram‐positive bacteria by targeting ribosomal RNA (rRNA), leading to protein misfolding. AGAs have predictable pharmacokinetics and often act in synergy with other antibiotics, such as beta‐lactams, making them powerful anti‐infective drugs (Hanberger et al. 2013 ). Despite their potential renal toxicity and ototoxicity and known bacterial resistance, diverse molecules of this family of antibiotics have been used in clinical practice for several decades (Thamban Chandrika and Garneau‐Tsodikova 2018

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  Biotechnology

  An Illustrated Primer

  • Rolf D. Schmid, Claudia Schmidt-Dannert, Ruth Hammelehle(Authors)
  • 2016(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Staphylococcus aureus strains (MRSA) (→204) (“first-line treatment”), the acylated glycopeptide teicoplanin and the lipopeptide daptomycin. The polyether antibiotic monensin is used in chicken feed, where it shows prophylactic efficacy against protozoa. Although nucleoside antibiotics occur naturally, only synthetic analogs are used in therapy, e. g., the guanosine analog acyclovir for the therapy of viral meningitis. The glycoside lincomycin is highly effective against Gram-positive enterobacteria.

  Glyco- and lipopeptide antibiotics. Vancomycin is produced by Amycolatopsis orientalis, an Actinomyces strain. It is used against penicillin-resistant Enterococci, e. g., in septic endocarditis, and for patients who are allergic to penicillin. Since it is nephrotoxic and has been or is sometimes used in combination with other nephrotoxic antibiotics, such as aminoglycosides and cyclosporin, thorough monitoring of nephrotoxic side-effects is absolutely required. The effect of vancomycin, like that of β-lactam antibiotics, relies on inhibition of bacterial cell wall biosynthesis (binding to UDP muramyl pentapeptide). Resistant strains form a modified cell wall glycopeptide that does not react with vancomycin. It is assumed that this type of resistance is horizontally transferred via transposons between humans and domestic animals. Teicoplanin is a mixture of glycolipids carrying various acyl side chains. Its broad spectrum of action is similar to that of vancomycin. Daptomycin is a cyclic peptide built from 11 amino acids and a decanoyl side-chain. It is produced by Streptomyces roseosporus and is presently (2014) among the safest antibiotics (i. e., to which the least resistance has been observed) and which can be used against infections even when vancomycin has failed. Daptomycin forms pores in bacterial cell membranes, resulting in the efflux of K+ ions and a depolarization of the membrane. Like vancomycin it must be applied parenterally. Cyclosporin A or cyclosporin is another cyclic lipopeptide. It is synthesized by fungi of the genus Beauveria.

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  Handbook of Carbohydrate-Modifying Biocatalysts

  • Peter Grunwald(Author)
  • 2016(Publication Date)
  • Jenny Stanford Publishing

    (Publisher)

  Although many successful antibiotics have been developed, due to the use of immunosuppressants, HIV/AIDS, drug abuse, etc., the immune defense of an increasing number of humans is weakened, with the consequence that multi-resistant variants of human pathogens emerged (Haebich and von Nussbaum, 2009, and literature cited therein). Tuberculosis is an example, an infection disease that is not at all defeated as documented by the 1.7 million deaths caused by this infection per year (WHO report 2008).

  In the following, mainly aminoglycoside antibiotics are discussed in some more detail as they are among the most commonly used broad-spectrum antibiotics, although there are several other classes of (amino)sugar-containing antibiotics, e.g., those belonging to the group of macrolide antibiotics (Fig. 2.10 ) or Glycopeptide Antibiotics, the biosynthesis of which has been reviewed by Yim et al., 2014, like vancomycin (Fig. 2.9 ). Amphotericin B (AmB 1, opposite box) is an example of a member of the polyene antibiotics. This antifungal drug, first isolated from Streptomyces nodosus, contains as a characteristic structural element 7 conjugated double bonds in all-trans configuration. It interacts with the cell membrane constituent ergosterol, which gives rise to the formation of transmembrane channels with subsequent leakage of predominantly K+ and H+ , leading to cell death (for more details see Paquet et al., 2006, and literature cited therein). The amino sugar mycosamine (3-amino- 3,6-dideoxymannose), attached to the polyene was found to be important for controlling the interaction of AmB 1 with ergosterol (Matsumori et al., 2005). After its detection in the early fifties of the last century, it was for a long time the most important drug for treatment of systemic mycoses.

  Figure 2.9 Structures of Streptomycin A, Kanamycin A, and Gentamicin C1. The syllable before last of naturally occurring aminoglycosides is written with "y" if they are produced by streptomyces strains (and with "i" if the producer is a Micromonospora

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  Handbook of Biologically Active Peptides

  • Abba Kastin(Author)
  • 2013(Publication Date)
  • Academic Press

    (Publisher)

  Willey JM, van der Donk WA. Lantibiotics: peptides of diverse structure and function. Annu Rev Microbiol. 2007;61:477–501. Chapter 20 Microcins Sylvie Rebuffat ABSTRACT Microcins are gene-encoded antimicrobial peptides (molecular weights <10 kDa) produced by Gram-negative bacteria, essentially Enterobacteria. They belong to a large class of bacteriocins and are involved in microbial competition. Microcins are highly stable peptides that display heterogeneous structures arising from various and complex posttranslational modifications acquired through specific enzyme machineries. These modifications include heterocycles (thiazole, oxazole), and nucleotide, or siderophore entities that contribute to the potent activity exerted by microcins toward bacterial species generally closely related to the producing bacteria. Most microcins use subtle Trojan horse strategies to kill sensitive bacteria: they either hijack iron siderophore receptors to enter cells or require processing when inside target bacteria to generate the toxic species. Subsequently, some inhibit strategic intracellular enzymes and functions (DNA gyrase, RNA polymerase, ATP-synthase, mRNA translation); others act at the cytoplasmic membrane level. Therefore, microcins provide fascinating models for novel antimicrobial strategies that evade common resistance mechanisms. Discovery and Classification Most bacteria and archaea produce an arsenal of toxic peptides and proteins, which are major actors of microbial competition. They are called bacteriocins, a term first introduced by François Jacob in the 1950s and further used to define proteinaceous compounds of bacterial origin that are lethal to bacteria differing from the producing strain

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  Genetics and Biochemistry of Antibiotic Production

  • Colin Stuttard, L. Vining(Authors)
  • 2014(Publication Date)
  • Butterworth-Heinemann

    (Publisher)

  Uttley, A.H.C., Collins, C.H., Naidoo, J. et al. (1988) Lancet pp. 57-58. Verna, A.K., Prakash, R., Annapurnaiah, P. et al. (1986) Abstracts, 26th Interscience Conference on Antimicrobial Agents and Chemotherapy, No. 941. Williamson, R., Al-Obeid, S. and Shlaes, J.A. (1989)7. Infect. Dis. 159, 1095-1104. Woodford, N., Johnson, A.P., Morrison, D. et al. (1990) Lancet 335, 226. Zmijewski, M.J. and Briggs, B. (1989) FEMS Microbiol. Lett. 59, 129-134. Zmijewski, M.J., Briggs, B., Logan, R. et al. (1987) Antimicrob. Agents. Chemother. 31, 1497-1501. This page intentionally left blank CHAPTER 10 Lantibiotics MJ. Gasson 10.1 INTRODUCTION Lantibiotics are polypeptides which, as their collective designation suggests, characteristically contain lanthionine residues. They have a polycyclic structure in which the rings are formed by m^o-lanthionine or /3-methyllanthionine interchain sulphide bridges. Most of the characterised lantibiotics exhibit antimicrobial properties but these molecules differ from other peptide antibiotics in that they are not synthesised solely by enzyme systems. Rather they are produced by post-translational modification of a primary gene product, which is referred to as a prelantibiotic. This consists of an amino-terminal leader sequence followed by a prolantibiotic region that contains amino acid residues equivalent to those in the mature lantibiotic. Cysteine, serine and threonine in the prolantibiotic region are the targets for post-translational modification. Serine and threonine can be dehydrated to produce dehydroalanine and dehydrobutyrine, respectively, and subsequent condensation of the dehydroamino acids with cysteine introduces the sulphide bridges to form mestf-lanthionine and /3-methyllanthionine (Figure 10-1).

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