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Antibiotic mode of action uncovered: halting RNA polymerase to tackle tuberculosis

Cryo-electron microscopy reveals the mechanism of action of fidaxomicin, a finding that could lead to the development of novel antibiotics.

Go to the profile of Benjamin Walden
Mar 22, 2018
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4 Comments

Go to the profile of Richard H. Ebright
Richard H. Ebright 5 months ago

The following statements are  false: 

(1) "In tuberculosis, RNAP only functions in the presence of an RbpA protein,." 

[M. tuberculosis RNAP is functional in the absence of RbpA.]

(2)"the drug had no effect on bacteria where RbpA was not required for RNAP action."

[Fidaxomicin potently kills bacteria that do not possess RpbA.  Fidaxomicin potently kills--and is in current clinical use against--Clostridium difficile, which does not possess RpbA.  Fidaxomicin also potently kills--and is under assessment for possible clinical use against--other major Gram-positive bacterial pathogens, including Staphylococci and Streptococci, which also do not possess RpbA.  Fidaxomicin also potently kills permeabilized strains of Gram-negtive bacterial pathogens, which also do not possess RpbA.  (Only a very narrow subset of bacterial species possesses RpbA.)]



Go to the profile of Benjamin Walden
Benjamin Walden 5 months ago

Hi Richard, 

Thank you for pointing this out! The article has now been updated to reflect these corrections.
If you have any more comments or queries please feel free to message me or the editor, Jasmine, or email editor@medchemnet.com. 

Thanks,
Ben Walden 

Go to the profile of Richard H. Ebright
Richard H. Ebright 5 months ago

Thank you for your responsivenness.

Unfortunately, the corrected version contains new errors:

"By competitively inhibiting the transcription factor, fidaxomicin stops RNAP  securing DNA, which inhibits transcription."

[First, fidaxomcin does not competitively inhibit the transcription factor RpbA.  Second, fidaxomicin traps an open-clamp state, inhibits stable DNA binding, and inhibits transcription through direct interactions with RNAP;  the transcription factor RpbA is neither necessary for, nor sufficient for, these effects.]


Go to the profile of Jasmine Harris
Jasmine Harris 5 months ago

Thank you for your comments. We really appreciate your engagement.