Enhanced antibiotic resistance development from fluoroquinolone persisters after a single exposure to antibiotic
Enhanced antibiotic resistance development from fluoroquinolone persisters after a single exposure to antibiotic
复制标题
DOI：
10.1038/s41467-019-09058-4
复制
发表时间：
2019-03-12
影响因子：
16.6
通讯作者：
Brynildsen, Mark P.
中科院分区：
文献类型：
--
作者：
Barrett, Theresa C.;Mok, Wendy W. K.;Brynildsen, Mark P.
细菌持久者能够耐受高水平的抗生素，并产生新的种群。持久耐受通常归因于最低限度的活跃细胞过程，以防止抗生素诱导的损害，这导致了这样的假设，即持久后代产生耐药突变的比率与正常细胞相当。使用时间推移显微镜监测氧氟沙星治疗后的大肠杆菌种群，我们发现持久者在恢复正常外观之前广泛地形成丝状并诱导令人印象深刻的SOS反应。此外，来自氟喹诺酮类持久者的群体比来自未经处理的对照组的群体含有更多数量的抗生素耐药突变。我们确认耐药性是可遗传的，这种增强需要RecA、SOS诱导、从治疗中恢复的机会以及容易出错的DNA聚合酶V(UmuDC)的参与。这些发现表明，氟喹诺酮类药物损害了持续者的DNA，随后的SOS反应加速了这些幸存者对抗生素的耐药性的发展。
Bacterial persisters are able to tolerate high levels of antibiotics and give rise to new populations. Persister tolerance is generally attributed to minimally active cellular processes that prevent antibiotic-induced damage, which has led to the supposition that persister offspring give rise to antibiotic-resistant mutants at comparable rates to normal cells. Using time-lapse microscopy to monitor Escherichia coli populations following ofloxacin treatment, we find that persisters filament extensively and induce impressive SOS responses before returning to a normal appearance. Further, populations derived from fluoroquinolone persisters contain significantly greater quantities of antibiotic-resistant mutants than those from untreated controls. We confirm that resistance is heritable and that the enhancement requires RecA, SOS induction, an opportunity to recover from treatment, and the involvement of error-prone DNA polymerase V (UmuDC). These findings show that fluoroquinolones damage DNA in persisters and that the ensuing SOS response accelerates the development of antibiotic resistance from these survivors.