Structure and mechanism of action of teicoplanin

Parenti, Francesco

doi:10.1016/0195-6701(86)90011-3

Cited by 76 publications

(38 citation statements)

References 11 publications

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“…These compounds possess antimicrobial activity by virtue of an ability to bind lipid II, the essential building block required for peptidoglycan, and therefore cell wall, synthesis [16,17]. To fully appreciate the consequences of lipid II binding one needs to appreciate the role of lipid II in peptidoglycan/cell wall formation.…”

Section: Vancomycin Resistancementioning

confidence: 99%

Discovery of Medically Significant Lantibiotics

Piper

Cotter²,

Ross³

et al. 2009

CDDT

112

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The emergence of drug-resistant pathogens such as staphylococci and enterococci in the hospital setting has long being recognized as a serious clinical problem. Staphylococcus aureus is the causative agent of many nosocomial infections from minor skin abscesses to serious, potentially life threatening diseases such as bone and soft tissue intra-surgical infections, sepsis and invasive endocarditis, while enterococci are responsible for nosocomial bacteraemia, surgical wound infections and endocarditis. The most infamous drug-resistant forms of these include MRSA (methicillin resistant S. aureus), VISA (vancomycin insensitive S. aureus), hVISA (heterogenous vancomycin insensitive S. aureus) and VRE (vancomycin resistant S. aureus). While enhanced hygiene awareness is essential to any solution, the identification of effective novel antimicrobial compounds remains a major goal in eradicating these and other infections caused by multi-drug resistant pathogens. In recent years a class of antimicrobial peptides, the Lantibiotics, have been the focus of an ever increasing level of attention. This interest has been prompted by an enhanced appreciation of the mode of action of these peptides (including, in many cases, the ability to bind lipid II) and their frequently high levels of antimicrobial activity. Here we review lantibiotic-related issues in drug discovery, outline the strategies that have been employed to identify these peptides and summarize the use of bioengineering to generate enhanced forms of these peptides as well as the application of the associated biological machinery to generate novel forms of existing pharmaceutical compounds. In so doing we highlight how some, or all, of these approaches have the potential to result in the development of clinically important drugs.

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Section: Vancomycin Resistancementioning

confidence: 99%

Discovery of Medically Significant Lantibiotics

Piper

Cotter²,

Ross³

et al. 2009

CDDT

112

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“…Some glycopeptides, including the teicoplanins (Figure 1) and the aridicins, have the amino group of an aminosugar substituted with a fatty acid chain containing nine to 11 carbon atoms (9). It is this substituent that confers greater hydrophobicity to the teicoplanin than to the vancomycin molecule, tt remains to be seen whether molecules with different or additional hydrophobic substituents are able to penetrate the outer membrane of gram-negative bacteria and thus increase the spectrum of activity of this important group of antibiotics.…”

Section: Structure Of Glycopeptidesmentioning

confidence: 99%

Structure, biochemistry and mechanism of action of glycopeptide antibiotics

Reynolds

1989

Eur. J. Clin. Microbiol. Infect. Dis.

626

401

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Glycopeptide antibiotics, including vancomycin and teicoplanin, are large, rigid molecules that inhibit a late stage in bacterial cell wall peptidoglycan synthesis. The three-dimensional structure contains a cleft into which peptides of highly specific configuration (L-aa-D-aa-D-aa) can fit: such sequences are found only in bacterial cell walls, hence glycopeptides are selectively toxic. Glycopeptides interact with peptides of this conformation by hydrogen bonding, forming stable complexes. As a result of binding to L-aa-D-Ala-D-Ala groups in wall intermediates, glycopeptides inhibit, apparently by steric hindrance, the formation of the backbone glycan chains (catalysed by peptidoglycan polymerase) from the simple wall subunits as they are extruded through the cytoplasmic membrane. The subsequent transpeptidation reaction that imparts rigidity to the cell wall is also thus inhibited. This unique mechanism of action, involving binding of the bulky inhibitor to the substrate outside the membrane so that the active sites of two enzymes cannot align themselves correctly, renders the acquisition of resistance to the glycopeptide antibiotics more difficult than that to the majority of the other antibiotic groups.

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“…Teicoplanin is a new glycopeptide antibiotic, chemically related to vancomycin (9). It is active against aerobic and anaerobic gram-positive bacteria only, including methicillin-resistant staphylococci, group D streptococci, Clostridium difficile, and group JK corynebacteria.…”

mentioning

confidence: 99%

Prospective randomized clinical trial of teicoplanin for empiric combined antibiotic therapy in febrile, granulocytopenic acute leukemia patients

Favero

Menichetti

Guerciolini

et al. 1987

Antimicrob Agents Chemother

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The increasing prevalence of bacteremia caused by gram-positive bacteria in granulocytopenic acute leukemia patients prompted us to evaluate, in a prospective randomized trial, the role of teicoplanin, a new glycopeptide antibiotic, when it was added to amikacin plus ceftazidime, as an empiric therapy of fever in these patients. Of 47 evaluable episodes, 22 were treated with the teicoplanin regimen and 25 were treated with the combination of amikacin and ceftazidime. The overall response to therapy of patients treated with teicoplanin was slightly better (82% improvement) than that obtained with amikacin plus ceftazidime (52%). The response rate of patients with gram-positive bacteremias was 80% (4 of 5) to the regimen that included teicoplanin; 25% (1 of 4) of the patients treated with amikacin plus ceftazidime responded to treatment; and for patients with gram-negative bacteremias, the response rates were, respectively, 100% (4 of 4) and 70% (7 of 10). The better results obtained with amikacin-ceftazidime-teicoplanin treatment were most evident in patients with profound (<100/mm3) and persistent neutropenia (83 versus 30% improvement). Furthermore, a good response rate of patients with gram-positive bacteremias (seven of eight; 87% improvement) was achieved in a small group of bone marrow transplant patients who were all treated with amikacin-ceftazidime-teicoplanin. No severe side effects were documented in any patient. Teicoplanin, as a drug administered as a single daily dose, seems to be a safe and useful anti-gram-positive agent when used in combination with amikacin-ceftazidime as an empiric therapy of febrile episodes in granulocytopenic acute leukemia patients.Changes in the relative prevalence of bacterial pathogens among granulocytopenic cancer patients have been observed in many centers and in numerous large clinical trials. Not only has the frequency of gram-positive bacteremias increased in recent years, but the clinical and microbiological picture of gram-positive infections has changed as well (6,8,10,12). The rmortality rate for these infections has increased (6), and many staphylococcal strains have become resistant to beta-lactam antibiotics and the aminoglycosides. Therefore, the antimicrobial regimens designed for empiric therapy in granulocytopenic patients, such as the combination of a beta-lactam and an aminoglycoside (2), do not satisfactorily cover the spectrum of gram-positive infections, especially those caused by methicillin-resistant strains of staphylococci or enterococci.A rational choice would be the addition of vancomycin or a similar drug to these regimens. Teicoplanin is a new glycopeptide antibiotic, chemically related to vancomycin (9). It is active against aerobic and anaerobic gram-positive bacteria only, including methicillin-resistant staphylococci, group D streptococci, Clostridium difficile, and group JK corynebacteria. Teicoplanin, therefore, has the same antibacterial spectrum that vancomycin has, with the added advantage of a long half-life, allowing once-a-day adm...

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Structure and mechanism of action of teicoplanin

Cited by 76 publications

References 11 publications

Discovery of Medically Significant Lantibiotics

Discovery of Medically Significant Lantibiotics

Structure, biochemistry and mechanism of action of glycopeptide antibiotics

Prospective randomized clinical trial of teicoplanin for empiric combined antibiotic therapy in febrile, granulocytopenic acute leukemia patients

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