Organization of the biosynthetic genes encoding deoxyactagardine B (DAB), a new lantibiotic produced by Actinoplanes liguriae NCIMB41362

Boakes, Steven; Appleyard, Antony N.; Cortés, Jesús M.; Dawson, Michael J.

doi:10.1038/ja.2010.48

Cited by 41 publications

(21 citation statements)

References 32 publications

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“…Because lantibiotics bind to lipid II at a site different from that affected by vancomycin and related glycopeptides, they are active against drug-resistant Gram-positive pathogens and have attracted attention as potential drug candidates (4,10).…”

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confidence: 99%

Efficacy of the New Lantibiotic NAI-107 in Experimental Infections Induced by Multidrug-Resistant Gram-Positive Pathogens

Jabès

Brunati

Candiani

et al. 2011

Antimicrob Agents Chemother

132

114

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NAI-107 is a novel lantibiotic active againstIn the granuloma pouch model induced in rats with a MRSA strain, intravenous NAI-107 showed a dose-proportional bactericidal activity that, at a single 40-mg/kg dose, compared with 2 20-mg/kg doses at a 12-h or 24-h interval, caused a 3-log 10 -CFU/ml reduction of viable MRSA in exudates that persisted for more than 72 h. Rat endocarditis was induced with a MRSA strain and treated for five consecutive days. In a first experiment, using 5, 10, or 20 mg/kg/day, and in a second experiment, when 10 mg/kg at 12-h intervals was compared to 20 mg/kg/day, intravenous NAI-107 was effective in reducing the bacterial load in heart vegetations in a dose-proportional manner. Trough plasma levels, as determined on days 2 and 5, were several times higher than the NAI-107 minimal bactericidal concentration (MBC). NAI-107 binding to rat and human serum ranges between 93% and 98.6%. The rapid bactericidal activity of NAI-107 observed in vitro was thus confirmed by the efficacy in several models of experimental infection induced by Gram-positive pathogens, supporting further investigation of the compound.

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mentioning

confidence: 99%

Efficacy of the New Lantibiotic NAI-107 in Experimental Infections Induced by Multidrug-Resistant Gram-Positive Pathogens

Jabès

Brunati

Candiani

et al. 2011

Antimicrob Agents Chemother

132

114

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“…The activity of mersacidin against MRSA makes it a potential candidate for development as a therapeutic agent. The actagardine group comprises actagardine A (Zimmermann et al 1995), deoxyactagardine B (Boakes et al 2010) and michiganin A (Holtsmark et al 2006). This group of compounds has in vitro antibacterial activity comparable to mersacidin and shares the mechanism of action by binding to lipid II, mediated very likely, by the ring containing the (Fig.…”

Section: Type B Lantibioticsmentioning

confidence: 98%

Lantibiotics and Similar Peptides Produced by and Active on Gram-Positives: Discovery, Development and Perspectives

Cortés¹

2013

Antimicrobials

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Lantibiotics are a group of ribosomally synthesised peptides that contain post-translational modifications consisting of (methyl)lanthionine residues forming bridges that confer them characteristic structures. Most lantibiotics are antibacterials that bind to the cell wall precursor lipid II. They can be rod shaped or globular depending on the distribution of the lanthionine residues. Their biosynthetic pathway is relatively simple when compared to other secondary metabolites. Due to this simplicity, genetic manipulation of the pathways is a very attractive tool to obtain variants that might have improved properties. Mutagenesis programmes have shown that the biosynthetic machinery of lantibiotics has relaxed specificity allowing the production of large collections of variants.

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“…2). This peptide has also 19 aa and differs from actagardine in residues 15 and 16 [actagardine contains valine (Val) and isoleucine (Ile) and deoxyactagardine, leucine (Leu) and Val, respectively] and by the absence of the sulfoxide bond in the MeLan bridge between residues 14 and 19 [68]. Semisynthetic derivatives of deoxyactagardine B, NVB302 and NVB333, display antimicrobial activity against important bacterial pathogens and are already in clinical trials.…”

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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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Organization of the biosynthetic genes encoding deoxyactagardine B (DAB), a new lantibiotic produced by Actinoplanes liguriae NCIMB41362

Cited by 41 publications

References 32 publications

Efficacy of the New Lantibiotic NAI-107 in Experimental Infections Induced by Multidrug-Resistant Gram-Positive Pathogens

Efficacy of the New Lantibiotic NAI-107 in Experimental Infections Induced by Multidrug-Resistant Gram-Positive Pathogens

Lantibiotics and Similar Peptides Produced by and Active on Gram-Positives: Discovery, Development and Perspectives

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

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