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TFA:

> Mechanistic studies of COE resistance

The evolution of bacterial resistance to COE2-2hexyl was analysed in S. Typhimurium and MRSA, using either serial dilution or morbidostat-based experimental evolution (see Methods). Serial dilution. No high-level COER mutants (≥50 × MIC) of either S. Typhimurium 14028 or CA-MRSA USA300 were isolated after serial dilution for 21 days; however, low-level COER mutants were recovered in both organisms (8 × MIC and 4 × MIC, respectively) (Supplementary Fig S1a; Supplementary Table S4a and b). Morbidostat. Although high-level CIPR mutants of wild-type E. coli (BW25113) were obtained after morbidostat culture for >3 days (64-128 × MIC),35 no COER mutants were observed under these conditions. Therefore, E. coli mutL (JW4128) and wild-type A. baumannii ATCC 17978 were assessed for COER mutants since both strains possess an inherently higher frequency of mutation (∼10-100-fold), resulting from deficiencies in either methyl-directed mismatch repair or the intrinsic DNA damage-inducible response, respectively.45,46 Only low-level COER mutants (2-4 × MIC) were recovered from either of these hypermutable strains, which is in marked contrast with the high-level CIPR mutants (128 × MIC) observed for A. baumannii35 (Supplementary Fig. S1b; Supplementary Table S4c–e).




That’s pretty much unreadable to someone not in the field. I’ve read it three times and still don’t know the answer to the GPs question. Yes I might be stupid, but I do have a biology degree.


More to it, from a layperson's point of view, that paragraph seems to contradict the headline. As they seemed to find COER mutants, albeit in low quantities, which I read as bacteria that could actually resist it?

Maybe they are saying that even though there are some bacteria that can resist it, they are never actually selected? But what would the mechanism for that be?


they recovered “low-level COER” mutants, maybe they can’t reproduce?

Edit: oh MIC is “minimum inhibitory concentration” so they only saw survivors with low levels of antibiotic.

Still, it seems reasonable to be skeptical, just because their tests did not find resistance does not prove it will never happen


I'm not skeptical or unskeptical. I just don't understand. My guess is that there's no construction if you understand what they are saying.


It sounds to me like they tried to make really easy to mutate bacteria develop resistance and failed to do so.




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