Department of Biology, Northeastern University, Boston, Massachusetts, USA.
J Bacteriol. 2013 Mar;195(6):1335-45. doi: 10.1128/JB.02176-12. Epub 2013 Jan 11.
Acinetobacter baumannii is an emerging nosocomial, opportunistic pathogen that survives desiccation and quickly acquires resistance to multiple antibiotics. Escherichia coli gains antibiotic resistances by expressing genes involved in a global response to DNA damage. Therefore, we asked whether A. baumannii does the same through a yet undetermined DNA damage response akin to the E. coli paradigm. We found that recA and all of the multiple error-prone DNA polymerase V (Pol V) genes, those organized as umuDC operons and unlinked, are induced upon DNA damage in a RecA-mediated fashion. Consequently, we found that the frequency of rifampin-resistant (Rif(r)) mutants is dramatically increased upon UV treatment, alkylation damage, and desiccation, also in a RecA-mediated manner. However, in the recA insertion knockout strain, in which we could measure the recA transcript, we found that recA was induced by DNA damage, while uvrA and one of the unlinked umuC genes were somewhat derepressed in the absence of DNA damage. Thus, the mechanism regulating the A. baumannii DNA damage response is likely different from that in E. coli. Notably, it appears that the number of DNA Pol V genes may directly contribute to desiccation-induced mutagenesis. Sequences of the rpoB gene from desiccation-induced Rif(r) mutants showed a signature that was consistent with E. coli DNA polymerase V-generated base-pair substitutions and that matched that of sequenced A. baumannii clinical Rif(r) isolates. These data strongly support an A. baumannii DNA damage-inducible response that directly contributes to antibiotic resistance acquisition, particularly in hospitals where A. baumannii desiccates and tenaciously survives on equipment and surfaces.
鲍曼不动杆菌是一种新兴的医院获得性机会致病菌，能够耐受干燥并迅速获得对多种抗生素的耐药性。大肠杆菌通过表达参与全球 DNA 损伤反应的基因获得抗生素耐药性。因此，我们想知道鲍曼不动杆菌是否通过一种尚未确定的类似于大肠杆菌模式的 DNA 损伤反应来实现这一点。我们发现，recA 和所有多个易错 DNA 聚合酶 V（Pol V）基因（那些组织为 umuDC 操纵子和不相关的基因），在 RecA 介导的方式下，在 DNA 损伤时被诱导。因此，我们发现 rifampin 抗性（Rif(r)）突变体的频率在 UV 处理、烷化损伤和干燥时显著增加，也是以 RecA 介导的方式。然而，在 recA 插入缺失突变株中，我们可以测量 recA 转录物，我们发现 recA 在 DNA 损伤时被诱导，而 uvrA 和一个不相关的 umuC 基因在没有 DNA 损伤时有些去阻遏。因此，调节鲍曼不动杆菌 DNA 损伤反应的机制可能与大肠杆菌不同。值得注意的是，似乎 DNA Pol V 基因的数量可能直接导致干燥诱导的突变。来自干燥诱导 Rif(r)突变体的 rpoB 基因序列显示出与大肠杆菌 DNA 聚合酶 V 产生的碱基对替换一致的特征，并且与测序的鲍曼不动杆菌临床 Rif(r)分离株相匹配。这些数据强烈支持鲍曼不动杆菌的 DNA 损伤诱导反应，该反应直接有助于抗生素耐药性的获得，特别是在医院中，鲍曼不动杆菌会干燥并顽强地存活在设备和表面上。
