Kumar Manoj, Rao Madhvi, Mathur Tarun, Barman Tarani Kanta, Joshi Vattan, Chaira Tridib, Singhal Smita, Pandya Manisha, Al Khodor Souhaila, Upadhyay Dilip J, Masuda Nobuhisa
Department of Microbiology, Daiichi Sankyo India Pharma Private Limited, Gurgaon, India.
Research Department, Sidra Medicine, Doha, Qatar.
Front Microbiol. 2021 Apr 23;12:603151. doi: 10.3389/fmicb.2021.603151. eCollection 2021.
forms biofilms in the lungs of chronically infected cystic fibrosis patients, which are tolerant to both the treatment of antibiotics and the host immune system. Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent efficacy in cystic fibrosis patients chronically infected with and improved their lung function. The present study was conducted to evaluate the effect of azithromycin on biofilm. We show that azithromycin exhibited a potent activity against biofilm, and microscopic observation revealed that azithromycin substantially inhibited the formation of solid surface biofilms. Interestingly, we observed that azithromycin restricted biofilm formation by inhibiting the expression of genes, which has been previously shown to play an essential role in bacterial attachment to solid-surface biofilm. In a rat model of chronic lung infection, we show that azithromycin treatment resulted in the suppression of quorum sensing-regulated virulence factors, significantly improving the clearance of biofilms compared to that in the placebo control. We conclude that azithromycin attenuates biofilm formation, impairs its ability to produce extracellular biofilm matrix, and increases its sensitivity to the immune system, which may explain the clinical efficacy of azithromycin in cystic fibrosis patients.
在慢性感染的囊性纤维化患者的肺部形成生物膜，这种生物膜对抗生素治疗和宿主免疫系统均具有耐受性。通常，抗生素对在生物膜中生长的细菌效果较差；阿奇霉素已显示出对慢性感染的囊性纤维化患者具有强效疗效，并改善了他们的肺功能。本研究旨在评估阿奇霉素对生物膜的影响。我们发现阿奇霉素对生物膜具有强效活性，显微镜观察显示阿奇霉素显著抑制了固体表面生物膜的形成。有趣的是，我们观察到阿奇霉素通过抑制基因的表达来限制生物膜的形成，此前已表明该基因在细菌附着于固体表面生物膜中起关键作用。在慢性肺部感染的大鼠模型中，我们表明阿奇霉素治疗导致群体感应调节的毒力因子受到抑制，与安慰剂对照组相比，显著提高了生物膜的清除率。我们得出结论，阿奇霉素可减弱生物膜的形成，损害其产生细胞外生物膜基质的能力，并增加其对免疫系统的敏感性，这可能解释了阿奇霉素在囊性纤维化患者中的临床疗效。
