SOS Response Induces Persistence to Fluoroquinolones in Escherichia coli

Abstract

Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli. Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic, in a manner dependent on the SOS gene network. These findings reveal an active and inducible mechanism of persister formation mediated by the SOS response, challenging the prevailing view that persisters are pre-existing and formed purely by stochastic means. SOS-induced persistence is a novel mechanism by which cells can counteract DNA damage and promote survival to fluoroquinolones. This unique survival mechanism may be an important factor influencing the outcome of antibiotic therapy in vivo.

RETRACTED: Bacterial persistence by RNA endonucleases

“…Moreover, cell populations enriched for persisters had increased levels of TA mRNAs (33,34), and deletion of yafQ (encoding a RelE homolog) resulted in reduced persistence of cells in a biofilm but not in planktonic cells (32). Interestingly, the type I TA locus tisAB/istR (36) was required for persister generation after induction of the SOS response (37,38). We show here that type II TA loci encoding mRNases are responsible for persister cell formation during exponential growth and during the stationary phase.…”

The toxin-antitoxin systemtisB-istR1

“…In 2009, Dörr et al 62 analyzed the effect of the fluoroquinolone ciprofloxacin on the formation of persisters. Fluoroquinolones are antibiotics that target DNA gyrase and DNA topoisomerase, ultimately causing DNA lesions which in turn trigger the SOS response.…”

“…The data suggested that these persister were not pre-existing but, at least mostly, were induced to enter this state. 62 E. coli encodes several SOS-induced TA systems (symE/symR, tisB/istR1, hokE/sokE, yafO/yafN, yafQ/dinJ 8 ), and TA genes had previously been found to be among the gene classes that were upregulated in persister cells. 56 In a follow-up paper by the Lewis group, it was shown that ciprofloxacin increased persister levels via SOS-dependent induction of TisB.…”

Molecular Background of Fluoroquinolone Resistance in Pathogenic Human Mycoplasmas

“…Прежде всего для многих бактерий альтернативой устойчивости является способ-ность адаптации к фторхинолонам, связанная с замедлением метаболизма, репликации ДНК и деления клеток, а также формированием биопленок [13,21,70,84].…”

“…Поскольку действие фторхинолонов на-правлено на ДНК, активация систем репара-ции важна для сохранения жизнеспособности [13,21,84]. Это было показано при исследо-вании влияния мутаций по гену ncr, продукт которого является репрессором системы репа-рации RecCBD, на устойчивость Acinetobacter baumannii к ципрофлоксацину.…”