Maudsdotter Lisa, Ushijima Yuri, Morikawa Kazuya
Department of Biomedical Science, University of Tsukuba, Tsukuba, Japan.
Front Microbiol. 2019 May 7;10:988. doi: 10.3389/fmicb.2019.00988. eCollection 2019.
Biofilms of accumulate cells resistant to the antibiotic rifampicin. We show here that the accumulation of rifampicin resistant mutants (RifR) in biofilms is not equable but rather is a local event, suggesting that the growth of a few locally emerged mutants is responsible for this. Competition assays demonstrated that, compared to wild-type bacteria, the isolated RifR mutants have a growth advantage in biofilms, but not in planktonic culture. To gain insight into the mechanism of the growth advantage, we tested the involvement of the two-component systems (TCS) that sense and respond to environmental changes. We found that a deletion of SrrAB or NreBC has a drastic effect on the growth advantage of RifR mutants, suggesting the importance of oxygen/respiration responses. All six of the RifR isolates tested showed increased resistance to at least one of the common stresses found in the biofilm environment (i.e., oxidative, nitric acid, and organic acid stress). The RifR mutants also had a growth advantage in a biofilm flow model, which highlights the physiological relevance of our findings.
生物膜会聚集对抗生素利福平具有抗性的细胞。我们在此表明，生物膜中利福平抗性突变体（RifR）的积累并非均匀分布，而是局部事件，这表明少数局部出现的突变体的生长是造成这种情况的原因。竞争试验表明，与野生型细菌相比，分离出的RifR突变体在生物膜中具有生长优势，但在浮游培养中则不然。为深入了解这种生长优势的机制，我们测试了感知并响应环境变化的双组分系统（TCS）的参与情况。我们发现，缺失SrrAB或NreBC会对RifR突变体的生长优势产生显著影响，这表明氧/呼吸反应的重要性。所测试的所有六个RifR分离株对生物膜环境中发现的至少一种常见应激（即氧化应激、硝酸应激和有机酸应激）的抗性均有所增加。RifR突变体在生物膜流动模型中也具有生长优势，这突出了我们研究结果的生理相关性。
