Kibdelins (AAD-609), novel glycopeptide antibiotics. II Isolation, purification and structure.

Folena-Wasserman, Gail; Poehland, B.; Yeung, E. W-K.; Staiger, David B.; Killmer, Lewis B.; Snader, Kenneth M.; Dingerdissen, John J.; Jeffs, Peter W.

doi:10.7164/antibiotics.39.1395

Cited by 26 publications

(6 citation statements)

References 13 publications

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“…The acyl groups were nundecanoic acid in PA and A and isododecanoic acid in PB and B. Among the glycopeptides, teicoplanin, aridicins, and kibdellins also contain fatty acid moieties (3,12,27). Another similarity between A40926 and the aridicins was the presence of two carboxylic acid functions which gave these molecules a net negative charge at neutral pH.…”

Section: Resultsmentioning

confidence: 99%

“…PA and PB, described here for the first time, predominated in the broth; during purification, these two compounds were largely converted to A and B, whose structures have been described recently (31a). One feature of all four factors, which relates them to teicoplanin and some other glycopeptides (aridicins and kibdellins) (3,27,12) while distinguishing them from vancomycin, ristocetin, and others, is the presence of a fatty acid moiety attached to one of the sugars. In terms of biological activity, the most striking difference between the components of the A40926 complex and other glycopeptide antibiotics is their activity against Neisseria gonorrhoeae.…”

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confidence: 99%

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A40926, a new glycopeptide antibiotic with anti-Neisseria activity

Goldstein¹,

Selva²,

Gastaldo³

et al. 1987

Antimicrob Agents Chemother

112

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In the course of a search for glycopeptide antibiotics having novel biological properties, we isolated A40926. Produced by an actinomycete of the genus Actinomadura, A40926 is a complex of four main factors which contain a fatty acid as part of a glycolipid attached to the peptide backbone. Its activity was, in most respects, similar to that of other glycopeptides, such as vancomycin and teicoplanin. However, in addition to inhibiting gram-positive bacteria, A40926 was very active against Neisseria gonorrhoeae. A40926 was rapidly bactericidal for N. gonorrhoeae clinical isolates at concentrations equal to or slightly higher than the MIC. In mice, levels in serum were higher and more prolonged than those of an equivalent subcutaneous dose of teicoplanin. These properties suggest that A40926 may have potential in the therapy of gonorrhea.The increased frequency of isolation of multiply antibioticresistant gram-positive bacteria has led to wider use of antibacterial agents which were originally rarely considered for first-line therapy, such as the glycopeptide vancomycin (18). One of the advantages of this antibiotic is that, thus far, resistance is rare and restricted to certain coagulase-negative staphylococci (25). The success of vancomycin has stimulated the development of new glycopeptides, such as teicoplanin (5,13,32,33). These antibiotics inhibit cell wall biosynthesis by binding to the D-alanyl-D-alanine portion of nascent peptidoglycan (22). Specific binding to an affinity resin containing acyl-D-alanyl-D-alanine groups (9) formed the basis of our search for new glycopeptides.Among the new glycopeptides identified, we focused our attention on those having novel biological properties. A40926 is the most interesting antibiotic which has emerged thus far from our screening campaign. In fermentation broths, we found it as a complex of four factors (PA, PB, A, and B). PA and PB, described here for the first time, predominated in the broth; during purification, these two compounds were largely converted to A and B, whose structures have been described recently (31a). One feature of all four factors, which relates them to teicoplanin and some other glycopeptides (aridicins and kibdellins) (3, 27, 12) while distinguishing them from vancomycin, ristocetin, and others, is the presence of a fatty acid moiety attached to one of the sugars. In terms of biological activity, the most striking difference between the components of the A40926 complex and other glycopeptide antibiotics is their activity against Neisseria gonorrhoeae.MATERIALS AND METHODS Isolation of A40926. We screened specifically for glycopeptide antibiotics by passing fermentation broths over the affinity resin Sepharose-D-alanyl-D-alanine (9) and eluting adsorbed glycopeptides with 1% aqueous ammonia. The strain producing A40926 was found in a soil sample collected in India. Batch adsorption to the same affinity resin described above yielded nearly pure A40926 complex in one step. Quick neutralization of the ammonia eluate yielded primarily the two fac...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

A40926, a new glycopeptide antibiotic with anti-Neisseria activity

Goldstein¹,

Selva²,

Gastaldo³

et al. 1987

Antimicrob Agents Chemother

112

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“…Several glycopeptides containing a long-chain aliphatic acyl residue on one of the amino sugars have been reported (8,9,19,32,39). Some of these compounds were reported to be superior in antibacterial activity and pharmacokinetics to vancomycin (10).…”

Section: Structure-activity Relationships (Sar)mentioning

confidence: 99%

Antibacterial activities and modes of action of vancomycin and related glycopeptides

Ramakrishnan

1991

Antimicrob Agents Chemother

130

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“…Members of the genus Kibdelosporangium , like Kibdelosporangium aridum subsp. largum and Kibdelosporangium philippinense , were found to produce antibiotics such as aridicins A [9], B and C [10], and kibdelins A, B [11], C and D [4], respectively.…”

Section: Full-textmentioning

confidence: 99%

Kibdelosporangium persicum sp. nov., a new member of the Actinomycetes from a hot desert in Iran

Safaei

Nouioui

Mast

et al. 2021

International Journal of Systematic and Evolutionary Microbiology

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Isolate 4NS15T was isolated from a neglected arid habitat in Kerman, Iran. The strain showed 16S rRNA gene sequence similarity values of 98.9 % to the type strains of Kibdelosporangium aridum subsp. aridum , Kibdelosporangium phytohabitans and Kibdelosporangium philippinense and 98.6 % to the type strain K. aridum subsp. largum , respectively. Genome-based phylogenetic analysis revealed that isolate 4NS15T is closely related to Kibdelosporangium aridum subsp. aridum DSM 43828T. The digital DNA–DNA hybridization value between the genome sequences of 4NS15T and strain DSM 43828T is 29.8 %. Strain 4NS15T produces long chains of spores without a sporangium-like structure which can be distinguished from other Kibdelosporangium species. Isolate 4NS15T has a genome size of 10.35 Mbp with a G+C content of 68.1 mol%. Whole-cell hydrolysates of isolate 4NS15T are rich in meso-diaminopimelic acid and cell-wall sugars such as arabinose, galactose, glucose and ribose. Major fatty acids (>10 %) are C16 : 0, iso-C16 : 0 and iso-C15 : 0. The phospholipid profile contains diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylhydroxyethanolamine, aminolipid and glycoaminolipid. The predominant menaquinone is MK-9(H4). Based on its phenotypic and genotypic characteristics, isolate 4NS15T (NCCB 100701=CIP 111705=DSM 110728) merits recognition as representing a novel species of the genus Kibdelosporangium , for which the name Kibdelosporangium persicum sp. nov. is proposed.

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Kibdelins (AAD-609), novel glycopeptide antibiotics. II Isolation, purification and structure.

Cited by 26 publications

References 13 publications

A40926, a new glycopeptide antibiotic with anti-Neisseria activity

A40926, a new glycopeptide antibiotic with anti-Neisseria activity

Antibacterial activities and modes of action of vancomycin and related glycopeptides

Kibdelosporangium persicum sp. nov., a new member of the Actinomycetes from a hot desert in Iran

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