Molecular characterization of lipid II pathway inhibitor-induced persistence phenotypes in Chlamydia and Wolbachia (A07)

胞内细菌衣原体和沃尔巴克氏菌是基因组高度减少的非模式生物。然而，它们合成了肽聚糖前体类脂II，并进化出不同的细胞分裂策略。在这两种细菌中，抑制糖基转移酶mray是肽聚糖前体脂质II生物合成的关键酶，导致扩大的未分裂细胞，这一表型在青霉素诱导的衣原体持续期间也可以看到。我们将阐明mray抑制剂的细胞效应，确定必要的过程和成分，包括非靶点，并定义是什么在细胞内细菌中打破持久性抗生素。

The intracellular bacteria Chlamydia and Wolbachia are non-model organisms with highly reduced genomes. Nevertheless, they synthesize the peptidoglycan precursor lipid II and evolved different strategies for cell division. In both endobacteria inhibition of the glycosyltransferase MraY, a key enzyme in the biosynthesis of the peptidoglycan precursor lipid II, results in enlarged non-dividing cells, a phenotype also seen during penicillin-induced persistence in Chlamydia. We will elucidate the cellular effects of MraY inhibitors, determine essential processes and components, including off-targets, and define what makes a persistence-breaking antibiotic in intracellular bacteria.