Lincomycin, clindamycin and their applications

Spížek, J.; Řezanka, Tomáš

doi:10.1007/s00253-003-1545-7

Cited by 165 publications

(66 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NMR studies revealed that this antibiotic compared with lincomycin exhibits higher affinity for the ribosome (3), in agreement with in vivo studies carried out in common pathogenic bacteria including Escherichia coli (1). In another study, however, the in vitro affinity of lincomycin to E. coli ribosomes was reported to be higher than that of clindamycin (4).…”

supporting

confidence: 72%

See 1 more Smart Citation

Unraveling New Features of Clindamycin Interaction with Functional Ribosomes and Dependence of the Drug Potency on Polyamines

Kouvela

Πετρόπουλος

Kalpaxis

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

The effect of spermine on the inhibition of peptide-bond formation by clindamycin, an antibiotic of the Macrolide-Lincosamide-Streptogramins B family, was investigated in a cell-free system derived from Escherichia coli. In this system peptide bond is formed between puromycin, a pseudo-substrate of the A-site, and acetylphenylalanyl-tRNA, bound at the P-site of poly(U)-programmed 70 S ribosomes. Biphasic kinetics revealed that one molecule of clindamycin, after a transient interference with the A-site of ribosomes, is slowly accommodated near the P-site and perturbs the 70 S/acetylphenylalanyl-tRNA complex so that a peptide bond is still formed but with a lower velocity compared with that observed in the absence of the drug. The above mechanism requires a high temperature (25°C as opposed to 5°C). If this is not met, the inhibition is simple competitive. It was found that at 25°C spermine favors the clindamycin binding to ribosomes; the affinity of clindamycin for the A-site becomes 5 times higher, whereas the overall inhibition constant undergoes a 3-fold decrease. Similar results were obtained when ribosomes labeled with N 1 -azidobenzamidinospermine, a photo-reactive analogue of spermine, were used or when a mixture of spermine and spermidine was added in the reaction mixture instead of spermine alone. Polyamines cannot compensate for the loss of biphasic kinetics at 5°C nor can they stimulate the clindamycin binding to ribosomes. Our kinetic results correlate well with photoaffinity labeling data, suggesting that at 25°C polyamines bound at the vicinity of the drug binding pocket affect the tertiary structure of ribosomes and influence their interaction with clindamycin.Lincomycin and clindamycin ( Fig. 1) are lincosamides, still used as therapeutic agents in human diseases and some animal infections. Clindamycin, a semisynthetic derivative of lincomycin (7(S)-chloro-7-deoxylincomycin), is usually more active than the parent compound in the treatment of bacterial infections, in particular those caused by anaerobic species (1).Lincosamides act on the large ribosomal subunit and share an overlapping binding site with macrolides, streptogramins B, chloramphenicol, and other antibiotics affecting the PTase 2 center, as deduced from competition experiments and crossresistance data (for review, see Ref.2) as well as from twodimensional transferred nuclear Overhauser effect spectroscopy analysis (3). In agreement with most of these observations, chemical footprinting analysis (4, 5) and crystallographic studies (6, 7) have revealed that lincosamides interact with both the A-site and the P-site on the 50 S ribosomal subunit and would be expected to hamper the positioning of aminoacyl moieties of tRNAs at both sites. This last view is consistent with earlier binding studies investigating the competition for binding to ribosomes between lincomycin and 3Ј-terminus pentanucleotide fragments from N-AcLeu-tRNA Leu , Leu-tRNA Leu , and Phe-tRNA Phe (8, 9) as well as with the finding that lincosamides stimulate oligopeptidy...

show abstract

supporting

confidence: 72%

“…1) are lincosamides, still used as therapeutic agents in human diseases and some animal infections. Clindamycin, a semisynthetic derivative of lincomycin (7(S)-chloro-7-deoxylincomycin), is usually more active than the parent compound in the treatment of bacterial infections, in particular those caused by anaerobic species (1).…”

mentioning

confidence: 99%

Unraveling New Features of Clindamycin Interaction with Functional Ribosomes and Dependence of the Drug Potency on Polyamines

Kouvela

Πετρόπουλος

Kalpaxis

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…When the drug was used alone, rapid emergence of resistance limited its use, except in association with another antistaphylococcal drug [20]. Clindamycin is a lincosamide antibiotic active against Gram-positive cocci and most anaerobic bacteria [21]. One trial found topical clindamycin superior to its vehicle [22], while another showed no difference between topical clindamycin and systemic tetracycline [23].…”

Section: Discussionmentioning

confidence: 99%

Combination Therapy with Clindamycin and Rifampicin for Hidradenitis Suppurativa: A Series of 116 Consecutive Patients

Géner¹,

Canouï‐Poitrine²,

Revuz³

et al. 2009

Dermatology

225

175

View full text Add to dashboard Cite

Background: Antibiotics are frequently used to treat hidradenitis suppurativa (HS); however, few data on their efficacy are available. Objective: To evaluate the efficacy of a combination of systemic clindamycin (300 mg twice daily) and rifampicin (600 mg daily) in the treatment of patients with severe HS. Methods: Patients (n = 116) who received this combination were studied retrospectively. The main outcome measure was the severity of the disease, assessed by the Sartorius score, before and after 10 weeks of treatment. Results: The Sartorius score dramatically improved at the end of treatment (median = 29, interquartile range = 14.5, vs. median = 14.5, interquartile range = 11; p < 0.001), as did other parameters of severity as well as the quality of life score. Eight patients (6.9%) stopped the treatment because of side effects. Conclusion: The combination of clindamycin and rifampicin is effective in the treatment of severe HS.

show abstract

“…The selected antibiotics range in their mode of antimicrobial activity including, inhibition of protein synthesis by preventing the binding of aminoacyl-t-RNA to the ribosomyl 30S subunit (tetracycline) [30] or by targeting the 23S rRNA by binding to the 50S ribosomal subunit (clindamycin), [31] inhibiting cell wall synthesis (vancomycin), [32] inactivating protein translation on the 50S ribosome during the peptidyl transferase step (chloramphenicol), [33] inhibiting DNA synthesis (ofloxacin), [34] inhibiting RNA synthesis by binding to RNA polymerase (rifampicin), [35] and interfering with cell wall permeability by binding to lipids on bacterial cytoplasmic membrane (colistin). [36] Combinations consisting of a cyclooctapeptide and one of these antibiotics, at their respective MICs, were tested [11] against E. coli and/or S. aureus based on the selectivity of the antibiotic for these bacteria.…”

Section: Synergistic Testingmentioning

confidence: 99%

In Vitro Synergy Between Some Cationic Amphipathic Cyclooctapeptides and Antibiotics

et al. 2015

View full text Add to dashboard Cite

The antimicrobial activities of some cationic amphipathic cyclooctapeptides in combination with select antibiotics are investigated. Accordingly, cyclooctapeptides (CPs 1-11) derived from the sequence cyclo[Leu-D-Leu-Leu-D-Leu-Lys-DLys-Lys-D-Lys] were tested against Escherichia coli and Staphylococcus aureus. Synergistic effects were evaluated in combination with tetracycline, chloramphenicol, oflaxacin, rifampicin, colistin, clindamycin, and vancomycin by the checkerboard titration assay. The results show that these cyclooctapeptides are fast acting bactericidals and are comparable to the related a-helical peptides in their activities. Significantly, some of these cyclooctapeptides exert selective synergistic effects in combination with the bacteriostatic tetracycline against S. aureus; a greater than 4-fold decrease in the minimum inhibition concentration was observed. Their synergism with the other evaluated antibiotics was generally partial or additive. Cationic amphipathic cyclooctapeptides in combination with some antibiotics could offer a possible solution to the increasing antimicrobial resistance predicament.

show abstract

Lincomycin, clindamycin and their applications

Cited by 165 publications

References 65 publications

Unraveling New Features of Clindamycin Interaction with Functional Ribosomes and Dependence of the Drug Potency on Polyamines

Unraveling New Features of Clindamycin Interaction with Functional Ribosomes and Dependence of the Drug Potency on Polyamines

Combination Therapy with Clindamycin and Rifampicin for Hidradenitis Suppurativa: A Series of 116 Consecutive Patients

In Vitro Synergy Between Some Cationic Amphipathic Cyclooctapeptides and Antibiotics

Contact Info

Product

Resources

About