Dokic Anja, Peterson Eliza, Arrieta-Ortiz Mario L, Pan Min, Di Maio Alessandro, Baliga Nitin, Bhatt Apoorva
School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Institute for Systems Biology, Seattle, WA 98109 USA.
Cell Surf. 2021 Apr 6;7:100051. doi: 10.1016/j.tcsw.2021.100051. eCollection 2021 Dec.
A non-tuberculous mycobacterium, is an emerging opportunistic pathogen associated with difficult to treat pulmonary infections, particularly in patients suffering from cystic fibrosis. It is capable of forming biofilms that result in an increase of already high levels of antibiotic resistance in this bacterium. Evidence that forms biofilm-like microcolonies in patient lungs and on medical devices further implicated the need to investigate this biofilm in detail. Therefore, in this study we characterized the pellicular biofilm, formed on a liquid-air interface, by studying its molecular composition, and its transcriptional profile in comparison to planktonic cells. Using scanning electron micrographs and fluorescence microscopy, we showed that biofilms produce an extracellular matrix composed of lipids, proteins, carbohydrates and extracellular DNA. Transcriptomic analysis of biofilms revealed an upregulation of pathways involved in the glyoxylate shunt, redox metabolism and mycolic acid biosynthesis. Genes involved in elongation and desaturation of mycolic acids were highly upregulated in biofilms and, mirroring those findings, biochemical analysis of mycolates revealed molecular changes and an increase in mycolic acid chain length. Together these results give us an insight into the complex structure of biofilms, the understanding of which may be adapted for clinical use in treatment of biofilm infections, including strategies for dispersing the extracellular matrix, allowing antibiotics to gain access to bacteria within the biofilm.
非结核分枝杆菌是一种新兴的机会性病原体，与难以治疗的肺部感染有关，尤其是在患有囊性纤维化的患者中。它能够形成生物膜，导致这种细菌本就很高的抗生素耐药性进一步增加。在患者肺部和医疗设备上形成生物膜样微菌落的证据进一步表明需要详细研究这种生物膜。因此，在本研究中，我们通过研究其分子组成以及与浮游细胞相比的转录谱，对在液 - 气界面形成的膜状生物膜进行了表征。使用扫描电子显微镜图像和荧光显微镜，我们表明生物膜产生了一种由脂质、蛋白质、碳水化合物和细胞外DNA组成的细胞外基质。生物膜的转录组分析揭示了乙醛酸循环、氧化还原代谢和分枝菌酸生物合成相关途径的上调。参与分枝菌酸延长和去饱和的基因在生物膜中高度上调，与这些发现一致，分枝菌酸盐的生化分析揭示了分子变化以及分枝菌酸链长度的增加。这些结果共同让我们深入了解了生物膜的复杂结构，对其的理解可能适用于临床治疗生物膜感染，包括分散细胞外基质的策略，使抗生素能够接触到生物膜内的细菌。
