Chemical probing of virginiamycin M-promoted conformational change of the peptidyl-transferase domain

Vannuffel, P.; Giambattista, M. Di; Cocito, Carlo

doi:10.1093/nar/22.21.4449

Cited by 21 publications

(10 citation statements)

References 29 publications

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“…Quinupristin-dalfopristin is a combination of two synergistic components, a streptogramin A-type antibiotic (dalfopristin) and a streptogramin B-type antibiotic (quinupristin) in a 70:30 ratio. Both compounds bind the 23S rRNA of the 50S ribosomal subunit and inhibit protein synthesis [5,6]. Alone, each factor displays a moderate bacteriostatic activity, while the combination of both factors is often bactericidal [6].…”

Section: Introductionmentioning

confidence: 99%

Bactericidal activity of quinupristin-dalfopristin against strains of Staphylococcus aureus with the MLSB phenotype of resistance according to the erm gene type

Clarebout¹,

Nativelle

Bozdoğan³

et al. 2004

International Journal of Antimicrobial Agents

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Section: Introductionmentioning

confidence: 99%

Bactericidal activity of quinupristin-dalfopristin against strains of Staphylococcus aureus with the MLSB phenotype of resistance according to the erm gene type

Clarebout¹,

Nativelle

Bozdoğan³

et al. 2004

International Journal of Antimicrobial Agents

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“…More recently, an A2062C transversion has been associated with 16-membered macrolide and streptogramin resistance in Streptococcus pneumoniae (3). While no drug effects could be directly attributed to the A2062 site, raising the possibility that such an effect, if it exists, may be attributed to ribosomal protein (20), A2062 was shielded by virginiamycin M (a streptogramin A) in a mutant strain resistant to virginiamycin S (a streptogramin B) (28). The aforementioned features may explain why our mutant strains became resistant to 16-membered macrolides due to mutation at position 2062 and retained their susceptibility to lincomycin and clindamycin.…”

mentioning

confidence: 99%

Two New Point Mutations at A2062 Associated with Resistance to 16-Membered Macrolide Antibiotics in Mutant Strains of Mycoplasma hominis

Furneri¹,

Rappazzo

Musumarra³

et al. 2001

Antimicrob Agents Chemother

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We describe two mutants of Mycoplasma hominis PG-21 which show resistance to 16-membered macrolides but susceptibility to lincosamides, obtained by in vitro exposure to increasing doses of josamycin. The 23S rRNA gene showed that each had a mutation (A2062G and A2062T) corresponding to nucleotide 2062 in Escherichia coli, which was associated with the acquired phenotype.The genetic bases for macrolide-lincosamide-streptogramin B group resistance have been extensively studied for many bacteria (2, 4-6, 16, 18, 27, 29, 30, 32-34) and mycoplasmas (8, 14). In Mycoplasma pneumoniae (14,22), as well as in other microorganisms, resistance to erythromycin has been associated with point mutations (A-to-G transition) in the loop of domain V of the 23S rRNA (2, 4-6, 8, 16, 18, 27, 29, 30, 32). Specific residues within domain V of 23S rRNA are involved in the action of macrolide-lincosamide-streptogramin antibiotics and chloramphenicol (2-6, 8, 11, 14-18, 20, 27-30, 32). It is well known that Mycoplasma hominis and many other mycoplasmas are resistant to erythromycin but susceptible to 16-membered macrolides (josamycin and miocamycin) (1, 7-9, 19, 23) and lincosamides (23). Recently the natural resistance of M. hominis to erythromycin has been associated with a guanine-to-adenine transition in position 2057 (Escherichia coli numbering), located in the central loop of the 23S rRNA domain V (8), and such a transition is present in Mycoplasma flocculare and Mycoplasma hyopneumoniae, which are also resistant to erythromycin (24).These features encouraged us to investigate the ability of josamycin to select for resistance in M. hominis strains, in order to see whether the acquired resistance pattern includes either macrolides only or both macrolides and lincosamides and to establish a possible relationship between the resistant phenotype and the appearance of specific point mutations in the region coding for the peptidyl transferase loop in the 23S rRNA gene.The type strain M. hominis PG-21 was chosen for our study. The strain was grown in SP-4 broth (pH 7.0) (7,8,21,25,26,31). The MIC was determined by a broth microdilution assay as previously described (7-9, 23).For multistep selection for resistance, SP-4 broth medium containing doubling concentrations of josamycin was inoculated with strain PG-21, incubated at 37°C, and examined for growth each day. To test for the development of resistance, 0.1 ml of the culture was withdrawn from each tube every day and spread on an SP-4 agar plate containing 1 g of josamycin/ml. All the colonies growing on josamycin-agar were challenged with increasing concentrations of the drug in broth (from 16 to 128 g/ml). All selected mutants were single colony purified on SP-4 agar-josamycin and drug-free SP-4 agar. Resistance to josamycin was assayed after the microrganisms were repeatedly transferred to antibiotic-free media.Two resistant clones of the M. hominis PG-21 strain were obtained by the selection procedure outlined above and were found to be stably resistant. The resistance/susceptibi...

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“…Quinupristin-Dulfopristin (QD) inhibits protein synthesis in S. aureus by binding to the 50S ribosomal unit. However, reduced susceptibility to the QD combination in S. aureus has been noticed recently [56].…”

Section: Inhibitors Of Bacterial Translationmentioning

confidence: 99%

Surmounting antimicrobial resistance in the Millennium Superbug: Staphylococcus aureus

Saxena

Gomber

2010

Open Medicine

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AbstractStaphylococcus aureus is the third most dreaded pathogen posing a severe threat due to its refractory behavior against the current armamentarium of antimicrobial drugs. This is attributed to the evolution of an array of resistance mechanisms responsible for morbidity and mortality globally. Local and international travel has resulted in the movement of drug resistant S. aureus clones from hospitals into communities and further into different geographical areas where they have been responsible for epidemic outbreaks. Thus, there is a dire necessity to refrain further cross movement of these multidrug resistant clones across the globe. The plausible alternative to prevent this situation is by thorough implementation of regulatory aspects of sanitation, formulary usage and development of new therapeutic interventions. Various strategies like exploring novel antibacterial targets, high throughput screening of microbes, combinatorial and synthetic chemistry, combinatorial biosynthesis and vaccine development are being extensively sought to overcome multidrug resistant chronic Staphylococcal infections. The majority of the antibacterial drugs are of microbial origin and are prone to being resisted. Anti-staphylococcal plant natural products that may provide a new alternative to overcome the refractory S.aureus under clinical settings have grossly been unnoticed. The present communication highlights the new chemical entities and therapeutic modalities that are entering the pharmaceutical market or are in the late stages of clinical evaluation to overcome multidrug resistant Staphylococcal infections. The review also explores the possibility of immunity and enzyme-based interventions as new therapeutic modalities and highlights the regulatory concerns on the prescription, usage and formulary development in the developed and developing world to keep the new chemical entities and therapeutic modalities viable to overcome antimicrobial resistance in S. aureus.

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Chemical probing of virginiamycin M-promoted conformational change of the peptidyl-transferase domain

Abstract: ABSTRACT

Cited by 21 publications

References 29 publications

Bactericidal activity of quinupristin-dalfopristin against strains of Staphylococcus aureus with the MLSB phenotype of resistance according to the erm gene type

Bactericidal activity of quinupristin-dalfopristin against strains of Staphylococcus aureus with the MLSB phenotype of resistance according to the erm gene type

Two New Point Mutations at A2062 Associated with Resistance to 16-Membered Macrolide Antibiotics in Mutant Strains of Mycoplasma hominis

Surmounting antimicrobial resistance in the Millennium Superbug: Staphylococcus aureus

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