Mutation in the
            <i>Bacillus subtilis</i>
            RNA Polymerase β′ Subunit Confers Resistance to Lipiarmycin

Gualtieri, Maxime; Villain-Guillot, Philippe; Latouche, Jaqueline; Leonetti, Jean-Paul; Bastide, Lionel

doi:10.1128/aac.50.1.401-402.2006

Cited by 42 publications

(40 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such mutants have MICs that are raised Ն16-fold. In the latter report (142), mutations leading to reduced permeability (or efflux? ), as indicated by effects on MICs of other antibiotics, were also found.…”

Section: Enoyl-reductases Of Fas II the Enoyl-reductases Of Bacteriamentioning

confidence: 99%

“…Fidaxomicin is the generic name of an Actinoplanes product, variously known as lipiarmycin (Table 4), tiacumicin B, and difimicin, discovered in 1975 (289). It is a specific inhibitor of transcription by RNA polymerase (328,344), and in B. subtilis, it selects for resistant mutants mapping in rpoC (at a frequency of 2 ϫ 10 Ϫ6 in one report [344] and Ͻ10 Ϫ7 in another [although 2 such mutants were indeed selected and mapped] [142]). Such mutants have MICs that are raised Ն16-fold.…”

Section: Enoyl-reductases Of Fas II the Enoyl-reductases Of Bacteriamentioning

confidence: 99%

See 1 more Smart Citation

Challenges of Antibacterial Discovery

Silver¹

2011

Clin Microbiol Rev

1,109

961

View full text Add to dashboard Cite

SUMMARY The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.

show abstract

Section: Enoyl-reductases Of Fas II the Enoyl-reductases Of Bacteriamentioning

confidence: 99%

Section: Enoyl-reductases Of Fas II the Enoyl-reductases Of Bacteriamentioning

confidence: 99%

Challenges of Antibacterial Discovery

Silver¹

2011

Clin Microbiol Rev

1,109

961

View full text Add to dashboard Cite

show abstract

“…(i) Rifampin, rifapentine, rifaximin (27), CBR (4), lipiarmycin (10), and streptolydigin (30) are molecules that inhibit transcription in vitro and whose target has been genetically validated by the isolation of resistant mutants in the genes coding for the RNA polymerase. (ii) SB2 (2, 9) and ureidothiophene (3) are molecules that inhibit transcription in vitro, but no genetic data has proven that the target is the RNA polymerase.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibitory effects of the RNAP inhibitors on transcription were measured according to the method of Gualtieri et al (10) on toluene-permeabilized S. epidermidis cells. The template for these reactions was the endogenous S. epidermidis DNA, and the concentration necessary to inhibit 50% of the [5-3 H]UTP incorporation was calculated by using the LSW data analysis tool (MDL, San Leandro, CA).…”

Section: Methodsmentioning

confidence: 99%

In Vitro Activities of Different Inhibitors of Bacterial Transcription against Staphylococcus epidermidis Biofilm

Villain-Guillot

Gualtieri

Bastide³

et al. 2007

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Staphylococcus epidermidis is a major cause of nosocomial infections because of its ability to form biofilms on the surface of medical devices. Only a few antibacterial agents are relatively active against biofilms, and rifampin, a transcription inhibitor, ranks among the most effective molecules against biofilm-related infections. Whether this efficacy is due to advantageous structural properties of rifampin or to the fact that the RNA polymerase is a favorable target remains unclear. In an attempt to answer this question, we investigated the action of different transcription inhibitors against S. epidermidis biofilm, including the newest synthetic transcription inhibitors. This comparison suggests that most of the antibiotics that target the RNA polymerase are active on S. epidermidis biofilms at concentrations close to their MICs. One of these compounds, CBR703, despite its high MIC ranks among the best antibiotics to eradicate biofilm-embedded bacteria.

show abstract

“…Originally known as lipiarmycin A4, this compound was first discovered in 1975 produced by Actinoplanes deccanensis [Coronelli et al 1975]. The mechanism of action is inhibition of RNA transcription at the sigma subunit and mobile-clamp domain β' of the RNA polymerase [Gualtieri et al 2006;Tupin et al 2010]. The major metabolite of fidaxomicin, OP-1118, is also active against C. difficile and formed by hydrolysis of the isobutyryl ester located at the 4″ position of fidaxomicin .…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Safety and efficacy of fidaxomicin in the treatment of Clostridium difficile-associated diarrhea

Golan

Epstein

2012

Therap Adv Gastroenterol

View full text Add to dashboard Cite

Clostridium difficile-associated diarrhea (CDAD) is the most common cause of healthcare-associated diarrhea. The current recommended treatment regimens of metronidazole and vancomycin have not changed in nearly 25 years. Fidaxomicin, an exceedingly narrow spectrum macrolide antibiotic, was recently approved for the treatment of CDAD. In phase III clinical trials, fidaxomicin was noninferior to vancomycin in achieving clinical cure of CDAD. Furthermore, fidaxomicin was associated with fewer recurrences of CDAD compared with vancomycin in clinical trials. These results, combined with the ease of administration and a good safety profile, make fidaxomicin an attractive treatment option for treating CDAD.

show abstract

Mutation in the Bacillus subtilis RNA Polymerase β′ Subunit Confers Resistance to Lipiarmycin

Cited by 42 publications

References 7 publications

Challenges of Antibacterial Discovery

Challenges of Antibacterial Discovery

In Vitro Activities of Different Inhibitors of Bacterial Transcription against Staphylococcus epidermidis Biofilm

Safety and efficacy of fidaxomicin in the treatment of Clostridium difficile-associated diarrhea

Contact Info

Product

Resources

About