Trespidi Gabriele, Scoffone Viola Camilla, Barbieri Giulia, Riccardi Giovanna, De Rossi Edda, Buroni Silvia
Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy.
Antibiotics (Basel). 2020 Nov 24;9(12):841. doi: 10.3390/antibiotics9120841.
The worldwide spread of antimicrobial resistance highlights the need of new druggable cellular targets. The increasing knowledge of bacterial cell division suggested the potentiality of this pathway as a pool of alternative drug targets, mainly based on the essentiality of these proteins, as well as on the divergence from their eukaryotic counterparts. People suffering from cystic fibrosis are particularly challenged by the lack of antibiotic alternatives. Among the opportunistic pathogens that colonize the lungs of these patients, is a well-known multi-drug resistant bacterium, particularly difficult to treat. Here we describe the organization of its division cell wall () cluster: we found that 15 genes of the operon can be transcribed as a polycistronic mRNA from to and that its transcription is under the control of a strong promoter regulated by MraZ. J2315 FtsZ was also shown to interact with the other components of the divisome machinery, with a few differences respect to other bacteria, such as the direct interaction with FtsQ. Using an in vitro sedimentation assay, we validated the role of SulA as FtsZ inhibitor, and the roles of FtsA and ZipA as tethers of FtsZ polymers. Together our results pave the way for future antimicrobial design based on the divisome as pool of antibiotic cellular targets.
抗菌药物耐药性在全球范围内的传播凸显了新型可成药细胞靶点的必要性。对细菌细胞分裂的了解日益深入，这表明该途径作为替代药物靶点库具有潜力，主要基于这些蛋白质的必需性以及与真核生物对应物的差异。囊性纤维化患者尤其面临缺乏抗生素替代品的挑战。在这些患者肺部定植的机会性病原体中，是一种众所周知的多重耐药细菌，特别难以治疗。在这里，我们描述了其分裂细胞壁（）簇的组织：我们发现操纵子的15个基因可以从到转录为多顺反子mRNA，并且其转录受MraZ调控的强启动子控制。J2315 FtsZ还显示与分裂体机器的其他成分相互作用，与其他细菌相比有一些差异，例如与FtsQ的直接相互作用。使用体外沉降试验，我们验证了SulA作为FtsZ抑制剂的作用，以及FtsA和ZipA作为FtsZ聚合物系链的作用。我们的研究结果共同为未来基于分裂体作为抗生素细胞靶点库的抗菌药物设计铺平了道路。
