id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-281188-0cql96hu	Baquero, Fernando	Proximate and ultimate causes of the bactericidal action of antibiotics	2020-10-06		.txt	text/plain	8715	411	36	(1) only free drug is active against the target bacteria, and protein binding of the drug decreases the rate of killing 19 ; (2) there are structures (such as porins) and mechanisms facilitating drug uptake, but also barriers that prevent the drug from entering the cells 20 ; (3) the drug can be pumped out, so the concentration needed for killing takes longer to achieve 21, 22 ; (4) the antibiotics with weak target-binding affinity will take longer to achieve the doses necessary for killing than those with greater affinity 23 ; (5) the targeted function might increase in the presence of the drug, thereby compensating for the inhibition by the drug 24 ; (6) the target function corresponds to the build-up of a cellular structure with slow turnover, which increases the amount of time for the antibiotic to kill 25,26 ; (7) the cells repair the damage produced by the antibiotics at rates that differ between drugs 27 ; (8) the damaged bacteria have inducible antibiotic-deactivating mechanisms 28 ; (9) the bacteria use alternative metabolic pathways that, to some extent, bypass those inhibited by the antibiotic 29, 30 ; (10) antibiotics differ in the extent to which they induce reactive oxygen species (ROS; deleterious) or SOS (potentially protective) responses and thereby the rate at which they kill the exposed bacteria [31] [32] [33] [34] ; (11) members of the antibiotic-exposed populations are either www.nature.com/nrmicro not replicating or are replicating slowly, and as such are killed at lower rates than the more active members of the population or their death is delayed; (12) the antibiotics produce a kind of 'stationary phase' by activating the general RpoS-mediated stringent response 35 .	./cache/cord-281188-0cql96hu.txt	./txt/cord-281188-0cql96hu.txt