Microbial glycosylation of erythromycin A

Kuo, M. S.; Chirby, D. G.; Argoudelis, A. D.; Cialdella, J. I.; Coats, J. H.; Marshall, Vincent P.

doi:10.1128/aac.33.12.2089

Cited by 42 publications

(19 citation statements)

References 16 publications

(15 reference statements)

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“…Recently, a new glycosylated compound, 2'-(O-[P-D-glucopyranosyl])-erythromycin, was isolated from the culture broth of Streptomyces vendargensis (10). However, it is not clear whether this example is relevant to drug resistance in pathogens, since S. vendargensis is not a pathogenic bacterium.…”

Section: Discussionmentioning

confidence: 99%

“…Inactivating enzymes such as ,B-lactamase, acetyltransferase, phosphotransferase, adenyltransferase, and rRNA methylase have been demonstrated as antibiotic resistance mechanisms in pathogenic bacteria (4,9,10). Although there are many reports regarding microbial resistance to rifampin, only a single mechanism based on a mutational alteration of the target enzyme moiety, i.e., DNA-dependent RNA polymerase, has been investigated thoroughly (13,18).…”

Section: Discussionmentioning

confidence: 99%

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Inactivation of rifampin by Nocardia brasiliensis

Yazawa

Mikami

Maeda

et al. 1993

Antimicrob Agents Chemother

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Rifampin was glycosylated by a pathogenic species of Nocardia, i.e., Nocardia brasiliensis. The structures of two glycosylated compounds (RIP-1 and RIP-2) isolated from the culture broth of the bacterium were Rifamycins are members of the naphthalenic ansamycin group of antibiotics characterized by a 17-membered ansa chain (1,5,11,17 (Becton Dickinson, Cockeysville, Md.). One loopful of spores or mycelial fragments from the slant cultures of Nocardia spp. was inoculated into a 10-ml Erlenmeyer shake flask containing 5 ml of a seed medium (2% glucose-enriched brain heart infusion medium; Difco Laboratories, Detroit, Mich.) with 4-mm glass beads intended to reduce aggregation of the nocardial cells (21). The inoculated flasks were shaken at 250 rpm (5.8-cm stroke) for 4 days at 27°C. The mature seed cultures were used as inocula for the inactivation or MIC experiments. Other bacterial inocula were prepared by the method previously described (21).MIC determination. The MIC, defined as the lowest drug concentration causing complete inhibition of visible growth, was determined by an agar dilution method using MuellerHinton II agar medium to give final concentrations from 0.39 to 400 ,ug/ml. Drug-free plates were included as a bacterial growth control. The inoculum size of a test organism was adjusted to 107 CFU/ml for Nocardia spp. and 106 CFU/ml for other bacteria. The plates were spotted with a multipoint inoculator (A 400; Denly Instruments, Ltd., Sussex, England) that delivered 0.005 ml, resulting in a spot inoculum of approximately 5 x 104 CFU.Time course of rifampin inactivation. The mature seed cultures were inoculated at a 10% rate into 100-ml Erlenmeyer flasks containing 50 ml of brain heart infusion medium. Methanol-sterilized rifampin was added aseptically at a final concentration of 20 or 200 ,ug/ml. For determination of the rifampin concentration, 2 ml of the flask cultures was harvested at various time intervals and filtered. The pH of the filtrate was adjusted to 2.0 with 2 N HCl, and the filtrate was then extracted with 2 ml of ethyl acetate. After concentration of the extract in vacuo to dryness, 100 ,ul of methanol was added and 50 ,ul of the mixture was tested for antibacterial activity. The rifampin concentration was measured by the size of the inhibition zone on a lawn of Bacillus subtilis PCI 219 grown on nutrient agar (Difco) (15). Inactivation products were monitored by thin-layer chromatography (TLC) using CHCl3-MeOH (4:1) as a developing solvent. Although rifampin or its inactivation products were easily detected by their characteristic reddish brown spots on untreated TLC plates, the inactivation products were usually monitored additionally by a dual-wavelength TLC scanner (CS-91OM; Shimadzu Seisakujyo, Tokyo, Japan) at 238 nm. Growth was determined by measuring the dry weight of mycelia: specifically, 5 ml of the culture was harvested at 1313

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inactivation of rifampin by Nocardia brasiliensis

Yazawa

Mikami

Maeda

et al. 1993

Antimicrob Agents Chemother

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“…Analysis of the biochemical basis of the resistance indicates that ribosomal modification by means of methylation at specific sites in the 23S rRNA seems to be a quite general resistance mechanism (13,14,22,23). However, enzymatic activities capable of inactivating macrolides have not been detected in macrolide producers, although they have been reported in clinical isolates (11) and in some other streptomycetes (8,9,21).…”

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confidence: 97%

Role of glycosylation and deglycosylation in biosynthesis of and resistance to oleandomycin in the producer organism, Streptomyces antibioticus

et al. 1992

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Cell extracts of Streptomyces antibioticus, an oleandomycin producer, can inactivate oleandomycin in the presence of UDP-glucose. The inactivation can be detected through the loss of biological activity or by alteration in the chromatographic mobility of the antibiotic. This enzyme activity also inactivates other macrolides (rosaramicin, methymycin, and lankamycin) which contain a free 2'-OH group in a monosaccharide linked to the lactone ring (with the exception of erythromycin), but not those which contain a disaccharide (tylosin, spiramycin, carbomycin, josamycin, niddamycin, and relomycin). Interestingly, the culture supernatant contains another enzyme activity capable of reactivating the glycosylated oleandomycin and regenerating the biological activity through the release of a glucose molecule. It is proposed that these two enzyme activities could be an integral part of the oleandomycin biosynthetic pathway.

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“…, including S. ambofaciens. Macrolide inactivation can be due to different modifications, for instance phosphorylation (Marshall et al, 1989 ;O'Hara et al, 1989), glycosylation (Kuo et al, 1989 ;Cundliffe, 1992 ;Vilches et al, 1992) or esterification of the lactone ring (Ounissi & Courvalin, 1985 ;Arthur et al, 1986).…”

Section: Abbreviations : Mls Macrolide-lincosamide-streptogramin Typmentioning

confidence: 99%

Dispensable ribosomal resistance to spiramycin conferred by srmA in the spiramycin producer Streptomyces ambofaciens The EMBL/GenBank accession number for the nucleotide sequence described in this paper is AJ223970.

et al. 1999

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Streptomyces ambofaciens produces the macrolide antibiotic spiramycin, an inhibitor of protein synthesis, and possesses multiple resistance mechanisms to the produced antibiotic. Several resistance determinants have been isolated from S. ambofaciens and studies with one of them, srmA, which hybridized with ermE (the erythromycin-resistance gene from Saccharopolyspora erythraea), are detailed here. The nucleotide sequence of srmA was determined and the mechanism by which its product confers resistance was characterized. The SrmA protein is a methyltransferase which introduces a single methyl group into A-2058 (Escherichia coli numbering scheme) in the large rRNA, thereby conferring an MLS (macrolide-lincosamide-streptogramin type B) type I resistance phenotype. A mutant of S. ambofaciens in which srmA was inactivated was viable and still produced spiramycin, indicating that srmA is dispensable, at least in the presence of the other resistance determinants.

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Microbial glycosylation of erythromycin A

Cited by 42 publications

References 16 publications

Inactivation of rifampin by Nocardia brasiliensis

Inactivation of rifampin by Nocardia brasiliensis

Role of glycosylation and deglycosylation in biosynthesis of and resistance to oleandomycin in the producer organism, Streptomyces antibioticus

Dispensable ribosomal resistance to spiramycin conferred by srmA in the spiramycin producer Streptomyces ambofaciens The EMBL/GenBank accession number for the nucleotide sequence described in this paper is AJ223970.

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