2020
DOI: 10.1038/s41579-020-00443-1
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Proximate and ultimate causes of the bactericidal action of antibiotics

Abstract: During the past 85 years of antibiotic use, we have learned a great deal about how these 'miracle' drugs work. We know the molecular structures and interactions of these drugs and their targets and the effects on the structure, physiology and replication of bacteria. Collectively, we know a great deal about these proximate mechanisms of action for virtually all antibiotics in current use. What we do not know is the ultimate mechanism of action; that is, how these drugs irreversibly terminate the 'individuality… Show more

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Cited by 200 publications
(167 citation statements)
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References 140 publications
(166 reference statements)
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“…We feel it is highly unlikely large numbers of denatured proteins can be reconstituted, as there is no known biological process for restoring life to particles containing so many different denatured proteins in aggregates. In fact, large numbers of protein aggregates are a clear indication of death (Baquero and Levin, 2021). The claims of 'reversible aggregation' and 'protein aggresome' by some VBNC authors (Pu et al, 2019;Fu et al, 2020) and even those in the persister field (Dewachter et al, 2021;Huemer et al, 2021) are necessitated due to the failure to realize these former cell particles are dead as shown by their TEM (Fu et al, 2020) and protein aggregation data (Pu et al, 2019;Fu et al, 2020;Huemer et al, 2021).…”
Section: Errors In 'Viability' Based On Membrane Stainingmentioning
confidence: 99%
“…We feel it is highly unlikely large numbers of denatured proteins can be reconstituted, as there is no known biological process for restoring life to particles containing so many different denatured proteins in aggregates. In fact, large numbers of protein aggregates are a clear indication of death (Baquero and Levin, 2021). The claims of 'reversible aggregation' and 'protein aggresome' by some VBNC authors (Pu et al, 2019;Fu et al, 2020) and even those in the persister field (Dewachter et al, 2021;Huemer et al, 2021) are necessitated due to the failure to realize these former cell particles are dead as shown by their TEM (Fu et al, 2020) and protein aggregation data (Pu et al, 2019;Fu et al, 2020;Huemer et al, 2021).…”
Section: Errors In 'Viability' Based On Membrane Stainingmentioning
confidence: 99%
“…Song and Wood assumed that if cells lost their ability to grow or form visible colonies on media, they were not viable, i.e. dead (Baquero and Levin, 2021;Song and Wood, 2021). This begs the question about cells that produce only limited growth, i.e.…”
Section: Loss Of Culturability Does Not Equal Bacterial Deathmentioning
confidence: 99%
“…Los primeros, como los betalactámicos o las fluoroquinolonas, causan la muerte de las bacterias. A diferencia de ellos, los bacteriostáticos (macrólidos) tan solo detienen su crecimiento [ 49 ]. Este efecto, que se estudia habitualmente in vitro mediante las denominadas curvas de letalidad (miden la reducción de un inóculo bacteriano a lo largo del tiempo en un caldo de cultivo), puede diferir del que acontece in vivo , ya que entran en juego otros factores como la respuesta del complemento, la propia actividad bactericida del suero y el sistema inmunológico.…”
Section: Efecto Bactericida Y Actividad Intrínsecaunclassified