Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA.
Antimicrob Agents Chemother. 2021 May 18;65(6). doi: 10.1128/AAC.00232-21.
The worldwide distribution of genes found on plasmids and their presence on the chromosomes of aquatic bacteria, such as , one of the suspected sources, suggests an origin before the development of synthetic quinolones. However, their native function remains unknown. Previous work indicated that expression of in was induced by cold shock. To investigate its role further, we constructed single in-frame deletion mutants in and (the gene for cold shock protein) and a double mutant in and in ATCC 17562 to evaluate the response to different environmental conditions and stresses and to exposure to various DNA-damaging agents. We found that is involved in resistance to ciprofloxacin, levofloxacin, and mitomycin C and in the cold shock response in Moreover, Δ and Δ mutants showed slower growth when they were treated with bile salts at 37°C and then shifted to 15°C (cold shock) without bile salts in the medium, with the effect being stronger in the double mutant. This transition may mimic what happens when is ingested into the gastrointestinal tract and released in its natural environment. Cold shock and bile salts induced the expression of and DNA gyrase and topoisomerase IV genes. However, no induction was found in the Δ mutant, suggesting that the gene is involved in the response to DNA damage and nucleic acid secondary structure.
质粒上基因的全球分布及其在水生细菌染色体上的存在,如被怀疑的来源之一,表明其起源早于合成喹诺酮类药物的发展。然而,它们的天然功能仍然未知。先前的工作表明,冷休克诱导了 在 中的表达。为了进一步研究其作用,我们构建了 在 中的单个框内缺失突变体和 在 和 (冷休克蛋白基因)中的双突变体,以及 在 ATCC 17562 中的 和 ,以评估其对不同环境条件和应激的反应以及对各种 DNA 损伤剂的暴露。我们发现 参与了对环丙沙星、左氧氟沙星和丝裂霉素 C 的耐药性以及 在中的冷休克反应。此外,Δ 和 Δ 突变体在用胆汁盐在 37°C 处理然后在没有胆汁盐的培养基中转移到 15°C(冷休克)时生长较慢,在双突变体中效果更强。这种转变可能模拟了当 被摄入胃肠道并在其自然环境中释放时发生的情况。冷休克和胆汁盐诱导了 和 DNA 拓扑异构酶 IV 基因的表达。然而,在 Δ 突变体中没有发现诱导,这表明 基因参与了对 DNA 损伤和核酸二级结构的反应。