Gardimycin, a new antibiotic from Actionoplanes. III. Biological properties.

Arioli, V.; Berti, Marisa; Silvestri, L. G.

doi:10.7164/antibiotics.29.511

Cited by 28 publications

(14 citation statements)

References 4 publications

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“…Actagardine also inhibits cell wall biosynthesis (29) and is able to strongly inhibit the binding of mersacidin to M. luteus cells, indicating that both lantibiotics compete for a similar binding site (6). However, actagardine and its variant Ala(0)-actagardine show a different activity spectrum from mersacidin (2,30). Whereas mersacidin displays high antibacterial activity against M. luteus and Staphylococcus aureus, actagardine and its variant show good activity against streptococci.…”

Section: Discussionmentioning

confidence: 95%

Construction of an Expression System for Site-DirectedMutagenesis of the LantibioticMersacidin

Szekat

Jack

Skutlarek

et al. 2003

Appl Environ Microbiol

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The lantibiotic (i.e., lanthionine-containing antibiotic) mersacidin is an antimicrobial peptide of 20 amino acids which is produced by Bacillus sp. strain HIL Y-85,54728. Mersacidin inhibits bacterial cell wall biosynthesis by binding to the precursor molecule lipid II. The structural gene of mersacidin (mrsA) and the genes for the enzymes of the biosynthesis pathway, dedicated transporters, producer self-protection proteins, and regulatory factors are organized in a biosynthetic gene cluster. For site-directed mutagenesis of lantibiotics, the engineered genes must be expressed in an expression system that contains all of the factors necessary for biosynthesis, export, and producer self-protection. In order to express engineered mersacidin peptides, a system in which the engineered gene replaces the wild-type gene on the chromosome was constructed. To test the expression system, three mutants were constructed. In S16I mersacidin, the didehydroalanine residue (Dha) at position 16 was replaced with the Ile residue found in the closely related lantibiotic actagardine. S16I mersacidin was produced only in small amounts. The purified peptide had markedly reduced antimicrobial activity, indicating an essential role for Dha16 in biosynthesis and biological activity of mersacidin. Similarly, Glu17, which is thought to be an essential structure in mersacidin, was exchanged for alanine. E17A mersacidin was obtained in good yields but also showed markedly reduced activity, thus confirming the importance of the carboxylic acid function at position 17 in the biological activity of mersacidin. Finally, the exchange of an aromatic for an aliphatic hydrophobic residue at position 3 resulted in the mutant peptide F3L mersacidin; this peptide showed only moderately reduced activity.

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Section: Discussionmentioning

confidence: 95%

Construction of an Expression System for Site-DirectedMutagenesis of the LantibioticMersacidin

Szekat

Jack

Skutlarek

et al. 2003

Appl Environ Microbiol

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“…This lantibiotic is produced by Actinoplanes garbadinensis and Actinoplanes liguriae [54][55][56]. It is composed of 19 aa (1890 Da) and four intramolecular rings, one Lan and three MeLan, with the C-terminal MeLan oxidized to sulfoxide [57][58][59].…”

Section: Actagardine and Derivativesmentioning

confidence: 99%

“…In vivo tests using mice experimentally infected with Strep. pneumoniae or Streptococcus haemolyticus (formerly referred to as Diplococcus haemolyticus) showed that actagardine has an antimicrobial activity comparable to those of ampicillin and cephaloridine [54].…”

Section: Actagardine and Derivativesmentioning

confidence: 99%

Lantibiotics produced by Actinobacteria and their potential applications (a review)

Gomes¹,

Duarte²,

Bastos³

2017

Microbiology

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The phylum Actinobacteria, which comprises a great variety of Gram-positive bacteria with a high G+C content in their genomes, is known for its large production of bioactive compounds, including those with antimicrobial activity. Among the antimicrobials, bacteriocins, ribosomally synthesized peptides, represent an important arsenal of potential new drugs to face the increasing prevalence of resistance to antibiotics among microbial pathogens. The actinobacterial bacteriocins form a heterogeneous group of substances that is difficult to adapt to most proposed classification schemes. However, recent updates have accommodated efficiently the diversity of bacteriocins produced by this phylum. Among the bacteriocins, the lantibiotics represent a source of new antimicrobials to control infections caused mainly by Gram-positive bacteria and with a low propensity for resistance development. Moreover, some of these compounds have additional biological properties, exhibiting activity against viruses and tumour cells and having also potential to be used in blood pressure or inflammation control and in pain relief. Thus, lantibiotics already described in Actinobacteria exhibit potential practical applications in medical settings, food industry and agriculture, with examples at different stages of pre-clinical and clinical trials.

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“…Actagardine is most active against streptococci and obligate anaerobes and demonstrates efficacy in the treatment of experimental Streptococcuspyogenes infections (Arioli et al, 1976;Malabarba et al, 1990). In contrast, mersacidin which is active against staphylococci and streptococci, has attracted recent attention due to its in vivo activity against methicillin-resistant Staphylococcus aureus strains; its activity is comparable to that of vancomycin and suggests mersacidin may prove to be an alternative therapeutic agent for the treatment of staphylococcal infections (Chatterjee et al, 1992a).…”

Section: Biological Activity Of Type-b Lantibioticsmentioning

confidence: 99%

Biosynthesis and Biological Activities of Lantibiotics with Unique Post‐Translational Modifications

Sahl¹,

Jack²,

Bierbaum³

1995

European Journal of Biochemistry

152

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Lantibiotics are biologically active peptides which contain the thioether amino acid lanthionine as well as several other modified amino acids. They can be broadly divided into two groups on the basis of their structures : type-A lantibiotics are elongated, amphiphilic peptides, while type-B lantibiotics are compact and globular. In the last decade there has been a marked increase in research interest in these peptides due both to the novel biosynthetic mechanisms by which they are produced, as well as to their potential applications. Lantibiotics are synthesised on the ribosome as a prepeptide which undergoes several post-translational modification events, including dehydration of specific hydroxyl amino acids to form dehydroamino acids, addition of neighbouring sulfhydryl groups to form thioethers and, in specific cases, other modifications such as introduction of D-alanine residues from L-serine, formation of lysinoalanine bridges, formation of novel N-terminal blocking groups and oxidative decarboxylation of a Cterminal cysteine. The genetic elements responsible for these specific modification reactions encode unique enzymes with hitherto unknown reaction mechanisms. Production of these peptides also requires accessory proteins including processing proteases, translocators of the ATP-binding cassette transporter family, regulatory proteins and dedicated producer self-protection mechanisms. While the principle biological activity of most type-B lantibiotics appears to be directed at the inhibition of enzyme functions, the type-A lantibiotics kill bacterial cells by forming pores in the cytoplasmic membrane.Keywords. Lantibiotics ; structures and conformations ; genetics and biosynthesis ; modes of action ; antibiotic peptides.Lantibiotics are a group of unique antibiotic peptides which are produced by and primarily act on Gram-positive bacteria. The term lantibiotics was introduced as an abbreviation for lanthionine-containing antibiotic peptides ) and refers to the most prominent features of this group, which are the strong antibacterial activity and the intra-molecular rings formed by the thioether amino acids lanthionine (Lan) and 3-methyllanthionine (MeLan). In addition to these unusual residues, the dehydrated amino acids 2,3-didehydroalanine (Dha) and 2,3-didehydrobutyrine (Dhb) occur commonly in lantibiotics, whereas further modified residues such as lysinoalanine, S-aminOVinyl-D-CySteine, S-aminovinyl-D-methylcysteine and erythro-3-hydroxyaspartic acid are only found in individual peptides. These unusual amino acids are synthesised by post-translational side-chain modifications of ribosomally produced precursor peptides. It is the presence of these residues, their influence on the structure and activity of the peptides and their unique

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Gardimycin, a new antibiotic from Actionoplanes. III. Biological properties.

Cited by 28 publications

References 4 publications

Construction of an Expression System for Site-DirectedMutagenesis of the LantibioticMersacidin

Construction of an Expression System for Site-DirectedMutagenesis of the LantibioticMersacidin

Lantibiotics produced by Actinobacteria and their potential applications (a review)

Biosynthesis and Biological Activities of Lantibiotics with Unique Post‐Translational Modifications

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